1516 lines
214 KiB
Text
1516 lines
214 KiB
Text
<!DOCTYPE html>
|
|
<html xmlns="http://www.w3.org/1999/xhtml" xml:lang="en" class="no-js no-jr">
|
|
<head>
|
|
<!-- For pinger, set start time and add meta elements. -->
|
|
<script type="text/javascript">var ncbi_startTime = new Date();</script>
|
|
|
|
<!-- Logger begin -->
|
|
<meta name="ncbi_db" content="books">
|
|
<meta name="ncbi_pdid" content="book-part">
|
|
<meta name="ncbi_acc" content="NBK1418">
|
|
<meta name="ncbi_domain" content="gene">
|
|
<meta name="ncbi_report" content="reader">
|
|
<meta name="ncbi_type" content="fulltext">
|
|
<meta name="ncbi_objectid" content="">
|
|
<meta name="ncbi_pcid" content="/NBK1418/?report=reader">
|
|
<meta name="ncbi_pagename" content="Achromatopsia - GeneReviews® - NCBI Bookshelf">
|
|
<meta name="ncbi_bookparttype" content="chapter">
|
|
<meta name="ncbi_app" content="bookshelf">
|
|
<!-- Logger end -->
|
|
|
|
<!--component id="Page" label="meta"/-->
|
|
<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Achromatopsia - GeneReviews® - NCBI Bookshelf</title>
|
|
<meta charset="utf-8">
|
|
<meta name="apple-mobile-web-app-capable" content="no">
|
|
<meta name="viewport" content="initial-scale=1,minimum-scale=1,maximum-scale=1,user-scalable=no">
|
|
<meta name="jr-col-layout" content="auto">
|
|
<meta name="jr-prev-unit" content="/books/n/gene/achondroplasia/?report=reader">
|
|
<meta name="jr-next-unit" content="/books/n/gene/npab/?report=reader">
|
|
<meta name="bk-toc-url" content="/books/n/gene/?report=toc">
|
|
<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE">
|
|
<meta name="citation_inbook_title" content="GeneReviews® [Internet]">
|
|
<meta name="citation_title" content="Achromatopsia">
|
|
<meta name="citation_publisher" content="University of Washington, Seattle">
|
|
<meta name="citation_date" content="2018/09/20">
|
|
<meta name="citation_author" content="Susanne Kohl">
|
|
<meta name="citation_author" content="Herbert Jägle">
|
|
<meta name="citation_author" content="Bernd Wissinger">
|
|
<meta name="citation_author" content="Ditta Zobor">
|
|
<meta name="citation_pmid" content="20301591">
|
|
<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK1418/">
|
|
<meta name="citation_keywords" content="Complete Achromatopsia (Rod Monochromatism, Total Color Blindness)">
|
|
<meta name="citation_keywords" content="Incomplete Achromatopsia">
|
|
<meta name="citation_keywords" content="Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha'">
|
|
<meta name="citation_keywords" content="Cyclic AMP-dependent transcription factor ATF-6 alpha">
|
|
<meta name="citation_keywords" content="Cyclic nucleotide-gated channel alpha-3">
|
|
<meta name="citation_keywords" content="Cyclic nucleotide-gated channel beta-3">
|
|
<meta name="citation_keywords" content="Guanine nucleotide-binding protein G(t) subunit alpha-2">
|
|
<meta name="citation_keywords" content="Retinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma">
|
|
<meta name="citation_keywords" content="ATF6">
|
|
<meta name="citation_keywords" content="CNGA3">
|
|
<meta name="citation_keywords" content="CNGB3">
|
|
<meta name="citation_keywords" content="GNAT2">
|
|
<meta name="citation_keywords" content="PDE6C">
|
|
<meta name="citation_keywords" content="PDE6H">
|
|
<meta name="citation_keywords" content="Achromatopsia">
|
|
<link rel="schema.DC" href="http://purl.org/DC/elements/1.0/">
|
|
<meta name="DC.Title" content="Achromatopsia">
|
|
<meta name="DC.Type" content="Text">
|
|
<meta name="DC.Publisher" content="University of Washington, Seattle">
|
|
<meta name="DC.Contributor" content="Susanne Kohl">
|
|
<meta name="DC.Contributor" content="Herbert Jägle">
|
|
<meta name="DC.Contributor" content="Bernd Wissinger">
|
|
<meta name="DC.Contributor" content="Ditta Zobor">
|
|
<meta name="DC.Date" content="2018/09/20">
|
|
<meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK1418/">
|
|
<meta name="description" content="Achromatopsia is characterized by reduced visual acuity, pendular nystagmus, increased sensitivity to light (photophobia), a small central scotoma, eccentric fixation, and reduced or complete loss of color discrimination. All individuals with achromatopsia (achromats) have impaired color discrimination along all three axes of color vision corresponding to the three cone classes: the protan or long-wavelength-sensitive cone axis (red), the deutan or middle-wavelength-sensitive cone axis (green), and the tritan or short-wavelength-sensitive cone axis (blue). Most individuals have complete achromatopsia, with total lack of function of all three types of cones. Rarely, individuals have incomplete achromatopsia, in which one or more cone types may be partially functioning. The manifestations are similar to those of individuals with complete achromatopsia, but generally less severe.">
|
|
<meta name="og:title" content="Achromatopsia">
|
|
<meta name="og:type" content="book">
|
|
<meta name="og:description" content="Achromatopsia is characterized by reduced visual acuity, pendular nystagmus, increased sensitivity to light (photophobia), a small central scotoma, eccentric fixation, and reduced or complete loss of color discrimination. All individuals with achromatopsia (achromats) have impaired color discrimination along all three axes of color vision corresponding to the three cone classes: the protan or long-wavelength-sensitive cone axis (red), the deutan or middle-wavelength-sensitive cone axis (green), and the tritan or short-wavelength-sensitive cone axis (blue). Most individuals have complete achromatopsia, with total lack of function of all three types of cones. Rarely, individuals have incomplete achromatopsia, in which one or more cone types may be partially functioning. The manifestations are similar to those of individuals with complete achromatopsia, but generally less severe.">
|
|
<meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK1418/">
|
|
<meta name="og:site_name" content="NCBI Bookshelf">
|
|
<meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-gene-lrg.png">
|
|
<meta name="twitter:card" content="summary">
|
|
<meta name="twitter:site" content="@ncbibooks">
|
|
<meta name="bk-non-canon-loc" content="/books/n/gene/achm/?report=reader">
|
|
<link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK1418/">
|
|
<link href="https://fonts.googleapis.com/css?family=Archivo+Narrow:400,700,400italic,700italic&subset=latin" rel="stylesheet" type="text/css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/jatsreader/ptpmc_3.22/css/libs.min.css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/jatsreader/ptpmc_3.22/css/jr.min.css">
|
|
<meta name="format-detection" content="telephone=no">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css//books_print.min.css" type="text/css" media="print">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_reader.min.css" type="text/css">
|
|
<style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} .body-content h2, .body-content .h2 {border-bottom: 1px solid #97B0C8} .body-content h2.inline {border-bottom: none} a.page-toc-label , .jig-ncbismoothscroll a {text-decoration:none;border:0 !important} .temp-labeled-list .graphic {display:inline-block !important} .temp-labeled-list img{width:100%}</style>
|
|
|
|
<link rel="shortcut icon" href="//www.ncbi.nlm.nih.gov/favicon.ico">
|
|
<meta name="ncbi_phid" content="CE8CC80F7C82860100000000005F0048.m_5">
|
|
<meta name='referrer' content='origin-when-cross-origin'/><link type="text/css" rel="stylesheet" href="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/css/3852956/3849091.css"></head>
|
|
<body>
|
|
<!-- Book content! -->
|
|
|
|
|
|
<div id="jr" data-jr-path="/corehtml/pmc/jatsreader/ptpmc_3.22/"><div class="jr-unsupported"><table class="modal"><tr><td><span class="attn inline-block"></span><br />Your browser does not support the NLM PubReader view.<br />Go to <a href="/pmc/about/pr-browsers/">this page</a> to see a list of supported browsers<br />or return to the <br /><a href="/books/NBK1418/?report=classic">regular view</a>.</td></tr></table></div><div id="jr-ui" class="hidden"><nav id="jr-head"><div class="flexh tb"><div id="jr-tb1"><a id="jr-links-sw" class="hidden" title="Links"><svg xmlns="http://www.w3.org/2000/svg" version="1.1" x="0px" y="0px" viewBox="0 0 70.6 85.3" style="enable-background:new 0 0 70.6 85.3;vertical-align:middle" xml:space="preserve" width="24" height="24">
|
|
<style type="text/css">.st0{fill:#939598;}</style>
|
|
<g>
|
|
<path class="st0" d="M36,0C12.8,2.2-22.4,14.6,19.6,32.5C40.7,41.4-30.6,14,35.9,9.8"></path>
|
|
<path class="st0" d="M34.5,85.3c23.2-2.2,58.4-14.6,16.4-32.5c-21.1-8.9,50.2,18.5-16.3,22.7"></path>
|
|
<path class="st0" d="M34.7,37.1c66.5-4.2-4.8-31.6,16.3-22.7c42.1,17.9,6.9,30.3-16.4,32.5h1.7c-66.2,4.4,4.8,31.6-16.3,22.7 c-42.1-17.9-6.9-30.3,16.4-32.5"></path>
|
|
</g>
|
|
</svg> Books</a></div><div class="jr-rhead f1 flexh"><div class="head"><a href="/books/n/gene/achondroplasia/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="body"><div class="t">Achromatopsia</div><div class="j">GeneReviews® [Internet]</div></div><div class="tail"><a href="/books/n/gene/npab/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></div><div id="jr-tb2"><a id="jr-bkhelp-sw" class="btn wsprkl hidden" title="Help with NLM PubReader">?</a><a id="jr-help-sw" class="btn wsprkl hidden" title="Settings and typography in NLM PubReader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 512 512" preserveAspectRatio="none"><path d="M462,283.742v-55.485l-29.981-10.662c-11.431-4.065-20.628-12.794-25.274-24.001 c-0.002-0.004-0.004-0.009-0.006-0.013c-4.659-11.235-4.333-23.918,0.889-34.903l13.653-28.724l-39.234-39.234l-28.72,13.652 c-10.979,5.219-23.68,5.546-34.908,0.889c-0.005-0.002-0.01-0.003-0.014-0.005c-11.215-4.65-19.933-13.834-24-25.273L283.741,50 h-55.484l-10.662,29.981c-4.065,11.431-12.794,20.627-24.001,25.274c-0.005,0.002-0.009,0.004-0.014,0.005 c-11.235,4.66-23.919,4.333-34.905-0.889l-28.723-13.653l-39.234,39.234l13.653,28.721c5.219,10.979,5.545,23.681,0.889,34.91 c-0.002,0.004-0.004,0.009-0.006,0.013c-4.649,11.214-13.834,19.931-25.271,23.998L50,228.257v55.485l29.98,10.661 c11.431,4.065,20.627,12.794,25.274,24c0.002,0.005,0.003,0.01,0.005,0.014c4.66,11.236,4.334,23.921-0.888,34.906l-13.654,28.723 l39.234,39.234l28.721-13.652c10.979-5.219,23.681-5.546,34.909-0.889c0.005,0.002,0.01,0.004,0.014,0.006 c11.214,4.649,19.93,13.833,23.998,25.271L228.257,462h55.484l10.595-29.79c4.103-11.538,12.908-20.824,24.216-25.525 c0.005-0.002,0.009-0.004,0.014-0.006c11.127-4.628,23.694-4.311,34.578,0.863l28.902,13.738l39.234-39.234l-13.66-28.737 c-5.214-10.969-5.539-23.659-0.886-34.877c0.002-0.005,0.004-0.009,0.006-0.014c4.654-11.225,13.848-19.949,25.297-24.021 L462,283.742z M256,331.546c-41.724,0-75.548-33.823-75.548-75.546s33.824-75.547,75.548-75.547 c41.723,0,75.546,33.824,75.546,75.547S297.723,331.546,256,331.546z"></path></svg></a><a id="jr-fip-sw" class="btn wsprkl hidden" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-rtoc-sw" class="btn wsprkl hidden" title="Table of Contents"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M20,20h10v8H20V20zM36,20h44v8H36V20zM20,37.33h10v8H20V37.33zM36,37.33h44v8H36V37.33zM20,54.66h10v8H20V54.66zM36,54.66h44v8H36V54.66zM20,72h10v8 H20V72zM36,72h44v8H36V72z"></path></svg></a></div></div></nav><nav id="jr-dash" class="noselect"><nav id="jr-dash" class="noselect"><div id="jr-pi" class="hidden"><a id="jr-pi-prev" class="hidden" title="Previous page"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a><div class="pginfo">Page <i class="jr-pg-pn">0</i> of <i class="jr-pg-lp">0</i></div><a id="jr-pi-next" class="hidden" title="Next page"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div><div id="jr-is-tb"><a id="jr-is-sw" class="btn wsprkl hidden" title="Switch between Figures/Tables strip and Progress bar"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><rect x="10" y="40" width="20" height="20"></rect><rect x="40" y="40" width="20" height="20"></rect><rect x="70" y="40" width="20" height="20"></rect></svg></a></div><nav id="jr-istrip" class="istrip hidden"><a id="jr-is-prev" href="#" class="hidden" title="Previous"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M80,40 60,65 80,90 70,90 50,65 70,40z M50,40 30,65 50,90 40,90 20,65 40,40z"></path><text x="35" y="25" textLength="60" style="font-size:25px">Prev</text></svg></a><a id="jr-is-next" href="#" class="hidden" title="Next"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M20,40 40,65 20,90 30,90 50,65 30,40z M50,40 70,65 50,90 60,90 80,65 60,40z"></path><text x="15" y="25" textLength="60" style="font-size:25px">Next</text></svg></a></nav><nav id="jr-progress"></nav></nav></nav><aside id="jr-links-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">NCBI Bookshelf</div></div><div class="cnt lol f1"><a href="/books/">Home</a><a href="/books/browse/">Browse All Titles</a><a class="btn share" target="_blank" rel="noopener noreferrer" href="https://www.facebook.com/sharer/sharer.php?u=https://www.ncbi.nlm.nih.gov/books/NBK1418/"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 33 33" style="vertical-align:middle" width="24" height="24" preserveAspectRatio="none"><g><path d="M 17.996,32L 12,32 L 12,16 l-4,0 l0-5.514 l 4-0.002l-0.006-3.248C 11.993,2.737, 13.213,0, 18.512,0l 4.412,0 l0,5.515 l-2.757,0 c-2.063,0-2.163,0.77-2.163,2.209l-0.008,2.76l 4.959,0 l-0.585,5.514L 18,16L 17.996,32z"></path></g></svg> Share on Facebook</a><a class="btn share" target="_blank" rel="noopener noreferrer" href="https://twitter.com/intent/tweet?url=https://www.ncbi.nlm.nih.gov/books/NBK1418/&text=Achromatopsia"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 33 33" style="vertical-align:middle" width="24" height="24"><g><path d="M 32,6.076c-1.177,0.522-2.443,0.875-3.771,1.034c 1.355-0.813, 2.396-2.099, 2.887-3.632 c-1.269,0.752-2.674,1.299-4.169,1.593c-1.198-1.276-2.904-2.073-4.792-2.073c-3.626,0-6.565,2.939-6.565,6.565 c0,0.515, 0.058,1.016, 0.17,1.496c-5.456-0.274-10.294-2.888-13.532-6.86c-0.565,0.97-0.889,2.097-0.889,3.301 c0,2.278, 1.159,4.287, 2.921,5.465c-1.076-0.034-2.088-0.329-2.974-0.821c-0.001,0.027-0.001,0.055-0.001,0.083 c0,3.181, 2.263,5.834, 5.266,6.438c-0.551,0.15-1.131,0.23-1.73,0.23c-0.423,0-0.834-0.041-1.235-0.118 c 0.836,2.608, 3.26,4.506, 6.133,4.559c-2.247,1.761-5.078,2.81-8.154,2.81c-0.53,0-1.052-0.031-1.566-0.092 c 2.905,1.863, 6.356,2.95, 10.064,2.95c 12.076,0, 18.679-10.004, 18.679-18.68c0-0.285-0.006-0.568-0.019-0.849 C 30.007,8.548, 31.12,7.392, 32,6.076z"></path></g></svg> Share on Twitter</a></div></aside><aside id="jr-rtoc-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Table of Content</div></div><div class="cnt lol f1"><a href="/books/n/gene/?report=reader">Title Information</a><a href="/books/n/gene/toc/?report=reader">Table of Contents Page</a></div></aside><aside id="jr-help-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Settings</div></div><div class="cnt f1"><div id="jr-typo-p" class="typo"><div><a class="sf btn wsprkl">A-</a><a class="lf btn wsprkl">A+</a></div><div><a class="bcol-auto btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 200 100" preserveAspectRatio="none"><text x="10" y="70" style="font-size:60px;font-family: Trebuchet MS, ArialMT, Arial, sans-serif" textLength="180">AUTO</text></svg></a><a class="bcol-1 btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M15,25 85,25zM15,40 85,40zM15,55 85,55zM15,70 85,70z"></path></svg></a><a class="bcol-2 btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M5,25 45,25z M55,25 95,25zM5,40 45,40z M55,40 95,40zM5,55 45,55z M55,55 95,55zM5,70 45,70z M55,70 95,70z"></path></svg></a></div></div><div class="lol"><a class="" href="/books/NBK1418/?report=classic">Switch to classic view</a><a href="/books/NBK1418/pdf/Bookshelf_NBK1418.pdf">PDF (607K)</a><a href="/books/NBK1418/?report=printable">Print View</a></div></div></aside><aside id="jr-bkhelp-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Help</div></div><div class="cnt f1 lol"><a id="jr-helpobj-sw" data-path="/corehtml/pmc/jatsreader/ptpmc_3.22/" data-href="/corehtml/pmc/jatsreader/ptpmc_3.22/img/bookshelf/help.xml" href="">Help</a><a href="mailto:info@ncbi.nlm.nih.gov?subject=PubReader%20feedback%20%2F%20NBK1418%20%2F%20sid%3ACE8B5AF87C7FFCB1_0191SID%20%2F%20phid%3ACE8CC80F7C82860100000000005F0048.4">Send us feedback</a><a id="jr-about-sw" data-path="/corehtml/pmc/jatsreader/ptpmc_3.22/" data-href="/corehtml/pmc/jatsreader/ptpmc_3.22/img/bookshelf/about.xml" href="">About PubReader</a></div></aside><aside id="jr-objectbox" class="thidden hidden"><div class="jr-objectbox-close wsprkl">✘</div><div class="jr-objectbox-inner cnt"><div class="jr-objectbox-drawer"></div></div></aside><nav id="jr-pm-left" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Previous Page</text></svg></nav><nav id="jr-pm-right" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Next Page</text></svg></nav><nav id="jr-fip" class="hidden"><nav id="jr-fip-term-p"><input type="search" placeholder="search this page" id="jr-fip-term" autocorrect="off" autocomplete="off" /><a id="jr-fip-mg" class="wsprkl btn" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-fip-done" class="wsprkl btn" title="Dismiss find">✘</a></nav><nav id="jr-fip-info-p"><a id="jr-fip-prev" class="wsprkl btn" title="Jump to previuos match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK1418_"><span class="title" itemprop="name">Achromatopsia</span></h1><p class="contribs">Kohl S, Jägle H, Wissinger B, et al.</p><p class="fm-aai"><a href="#_NBK1418_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 38 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="achm.Summary" itemprop="description"><h2 id="_achm_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Achromatopsia is characterized by reduced visual acuity, pendular nystagmus, increased sensitivity to light (photophobia), a small central scotoma, eccentric fixation, and reduced or complete loss of color discrimination. All individuals with achromatopsia (achromats) have impaired color discrimination along all three axes of color vision corresponding to the three cone classes: the protan or long-wavelength-sensitive cone axis (red), the deutan or middle-wavelength-sensitive cone axis (green), and the tritan or short-wavelength-sensitive cone axis (blue). Most individuals have <i>complete achromatopsia</i>, with total lack of function of all three types of cones. Rarely, individuals have <i>incomplete achromatopsia</i>, in which one or more cone types may be partially functioning. The manifestations are similar to those of individuals with complete achromatopsia, but generally less severe.</p><p>Hyperopia is common in achromatopsia. Nystagmus develops during the first few weeks after birth followed by increased sensitivity to bright light. Best visual acuity varies with severity of the disease; it is 20/200 or less in complete achromatopsia and may be as high as 20/80 in incomplete achromatopsia. Visual acuity is usually stable over time; both nystagmus and sensitivity to bright light may improve slightly. Although the fundus is usually normal, macular changes (which may show early signs of progression) and vessel narrowing may be present in some affected individuals. Defects in the macula are visible on optical coherence tomography.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of achromatopsia is established in a proband through clinical and family history, examination for nystagmus, visual acuity testing, color vision assessment, and fundoscopic examination. If achromatopsia is suspected, additional testing may include optical coherence tomography, fundus autofluorescence, visual fields, and electroretinogram. Identification of biallelic pathogenic (or likely pathogenic) variants in <i>ATF6</i>, <i>CNGA3</i>, <i>CNGB3</i>, <i>GNAT2</i>, <i>PDE6C</i>, or <i>PDE6H</i> confirms the clinical diagnosis.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Dark or special filter glasses or red-tinted contact lenses to reduce photophobia and potentially improve visual acuity; low vision aids; preferential classroom seating for children; occupational aids.</p><p><i>Surveillance</i>: Ophthalmologic examination every six to 12 months for children and every two to three years for adults.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>Achromatopsia is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible if the pathogenic variants have been identified in the family.</p></div></div><div id="achm.GeneReview_Scope"><h2 id="_achm_GeneReview_Scope_"><i>GeneReview</i> Scope</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figachmTd"><a href="/books/NBK1418/table/achm.Td/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobachmTd"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="achm.Td"><a href="/books/NBK1418/table/achm.Td/?report=objectonly" target="object" rid-ob="figobachmTd">Table</a></h4><p class="float-caption no_bottom_margin">Complete achromatopsia (rod monochromatism, total color blindness) Incomplete achromatopsia</p></div></div></div><div id="achm.Diagnosis"><h2 id="_achm_Diagnosis_">Diagnosis</h2><div id="achm.Suggestive_Findings"><h3>Suggestive Findings</h3><p>Achromatopsia <b>should be suspected</b> in individuals with the following typical clinical findings, additional testing, and family history.</p><p>
|
|
<b>Clinical findings</b>
|
|
</p><ul><li class="half_rhythm"><div>Pendular nystagmus</div></li><li class="half_rhythm"><div>Increased sensitivity to light (photophobia)</div></li><li class="half_rhythm"><div>Eccentric fixation</div></li><li class="half_rhythm"><div>Reduced visual acuity</div></li><li class="half_rhythm"><div>Reduced or complete lack of color discrimination</div></li><li class="half_rhythm"><div>Small central scotoma</div></li><li class="half_rhythm"><div>Fundus appearance: normal in many affected individuals, but can show subtle bilateral macular changes such as absence of the foveal reflex, pigment mottling, or narrowing of the retinal vessels. Frank atrophy of the retinal pigment epithelium (RPE) in the fovea can occur in older individuals.</div></li></ul><p>
|
|
<b>Additional testing</b>
|
|
</p><p><b>Color vision tests.</b> The color perception of individuals with achromatopsia (achromats) is unreliable; many achromats learn to associate certain colors with objects and to recognize some colors by discerning differences in brightness [<a class="bibr" href="#achm.REF.sharpe.1999" rid="achm.REF.sharpe.1999">Sharpe et al 1999</a>]. In general, all achromats have anomalous (impaired) color discrimination along all three axes of color vision corresponding to the three cone classes: the protan or long-wavelength-sensitive cone axis (red), the deutan or middle-wavelength-sensitive cone axis (green), and the tritan or short-wavelength-sensitive cone axis (blue). The following results are found on standard testing for color vision:</p><ul><li class="half_rhythm"><div>Generally, no specific axis of color confusion is found on the Farnsworth Munsell 100-hue test.</div></li><li class="half_rhythm"><div>An achromat axis (in which the constituent color chips are arranged according to their rod-perceived lightness) is characteristic for complete achromatopsia on both the saturated and desaturated versions of the Panel D-15 test.</div></li><li class="half_rhythm"><div>The most important and diagnostic test is red-green color discrimination with the Rayleigh anomaloscope equation. Although a complete achromat can always fully color-match the spectral yellow primary to any mixture of the spectral red and green primaries, a brightness match is only possible to red primary-dominated mixtures.</div></li></ul><p><b>Visual field testing.</b> Small central scotomas can be demonstrated in some individuals by careful testing. However, unsteady fixation can make demonstration of a central scotoma difficult.</p><p>
|
|
<b>Electroretinogram (ERG)</b>
|
|
</p><ul><li class="half_rhythm"><div><b>Full-field ERG.</b> The photopic response (including the 30-Hz flicker response) is absent or markedly diminished; the scotopic response is normal or mildly abnormal.</div></li><li class="half_rhythm"><div><b>15-Hz flicker ERG.</b> A typical finding is absence of the cone-driven fast pathway response elicited by high flash intensities [<a class="bibr" href="#achm.REF.bijveld.2011.161" rid="achm.REF.bijveld.2011.161">Bijveld et al 2011</a>].</div></li></ul><p><b>Optical coherence tomography (OCT).</b> A variable degree of foveal hypoplasia as well as disruption and/or loss of inner-/outer-segment junction of the photoreceptors and an attenuation of the RPE layer within the macular region can be observed at an early age [<a class="bibr" href="#achm.REF.genead.2011.7298" rid="achm.REF.genead.2011.7298">Genead et al 2011</a>, <a class="bibr" href="#achm.REF.thomas.2011.882" rid="achm.REF.thomas.2011.882">Thomas et al 2011</a>, <a class="bibr" href="#achm.REF.sundaram.2014.234" rid="achm.REF.sundaram.2014.234">Sundaram et al 2014</a>, <a class="bibr" href="#achm.REF.lee.2015.2145" rid="achm.REF.lee.2015.2145">Lee et al 2015</a>, <a class="bibr" href="#achm.REF.zobor.2017.821" rid="achm.REF.zobor.2017.821">Zobor et al 2017</a>].</p><p><b>Fundus autofluorescence imaging</b> shows missing or variable formation of foveal hypofluorescence or a larger lesion with a surrounding hyperautofluorescent ring and a central region of absent autofluorescence corresponding to the lesion area seen on OCT [<a class="bibr" href="#achm.REF.greenberg.2014.437" rid="achm.REF.greenberg.2014.437">Greenberg et al 2014</a>, <a class="bibr" href="#achm.REF.kohl.2015.757" rid="achm.REF.kohl.2015.757">Kohl et al 2015</a>].</p><p><b>Adaptive optics imaging</b> shows remnant cone structure; however, the number and spatial distribution of the foveal cones are highly variable – the foveal cone mosaic ranges from a contiguously packed mosaic to a sparsely arranged collection of cones [<a class="bibr" href="#achm.REF.langlo.2016.3984" rid="achm.REF.langlo.2016.3984">Langlo et al 2016</a>].</p><p><b>Family history</b> is consistent with autosomal recessive inheritance.</p></div><div id="achm.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The clinical diagnosis of achromatopsia <b>is established</b> in a proband with typical findings on clinical examination, additional testing, and family history (see <a href="#achm.Suggestive_Findings">Suggestive Findings</a>). Identification of biallelic pathogenic (or likely pathogenic) variants in one of the six genes listed in <a href="/books/NBK1418/table/achm.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobachmTmoleculargenetictestingusedin">Table 1</a> establishes the molecular diagnosis.</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variant" and "likely pathogenic variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [<a class="bibr" href="#achm.REF.richards.2015.405" rid="achm.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this <i>GeneReview</i> is understood to include likely pathogenic variants. (2) Identification of biallelic variants of uncertain significance (or of one known pathogenic variant and one variant of uncertain significance) in one of the six genes listed in <a href="/books/NBK1418/table/achm.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobachmTmoleculargenetictestingusedin">Table 1</a> does not establish or rule out the diagnosis.</p><p>Molecular genetic testing approaches can include <b>targeted analysis</b> for the common <i>CNGB3</i> variant <a href="/books/NBK1418/table/achm.T.cngb3_pathogenic_variants_discuss/?report=objectonly" target="object" rid-ob="figobachmTcngb3pathogenicvariantsdiscuss">c.1148delC</a>, use of a <b>multigene panel</b>, or <b>comprehensive</b>
|
|
<b>genomic testing</b> (typically <b>exome sequencing</b>):</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Targeted analysis</b> for the most common pathogenic variant <a href="/books/NBK1418/table/achm.T.cngb3_pathogenic_variants_discuss/?report=objectonly" target="object" rid-ob="figobachmTcngb3pathogenicvariantsdiscuss">c.1148delC</a> in <i>CNGB3</i> can be performed first in European populations or populations of European descent in the US, Canada, Australia, and New Zealand (see Molecular Genetics, <a href="#achm.CNGB3"><i>CNGB3</i></a>, <b>Pathogenic variants</b>)<i>.</i></div></li><li class="half_rhythm"><div class="half_rhythm"><b>A multigene panel</b> that includes <i>ATF6</i>, <i>CNGA3</i>, <i>CNGB3</i>, <i>GNAT2</i>, <i>PDE6C</i>, <i>PDE6H</i>, and other genes of interest (see <a href="#achm.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Comprehensive</b>
|
|
<b>genomic testing</b> does not require the clinician to determine which gene[s] are likely involved. <b>Exome sequencing</b> is most commonly used; <b>genome sequencing</b> can also be used.</div><div class="half_rhythm">For an introduction to comprehensive genomic testing click <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing_1">here</a>.</div></li></ul><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figachmTmoleculargenetictestingusedin"><a href="/books/NBK1418/table/achm.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobachmTmoleculargenetictestingusedin"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="achm.T.molecular_genetic_testing_used_in"><a href="/books/NBK1418/table/achm.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobachmTmoleculargenetictestingusedin">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in Achromatopsia </p></div></div></div></div><div id="achm.Clinical_Characteristics"><h2 id="_achm_Clinical_Characteristics_">Clinical Characteristics</h2><div id="achm.Clinical_Description"><h3>Clinical Description</h3><p>Achromatopsia is characterized by reduced visual acuity, pendular nystagmus, increased sensitivity to light (photophobia), a small central scotoma (which is often difficult to demonstrate), eccentric fixation, and reduced or complete lack of color discrimination. Hyperopia is common. Nystagmus develops during the first few weeks after birth and is followed by increased sensitivity to bright light.</p><p>Best visual acuity varies with severity of the disease; it is 20/200 or less in complete achromatopsia and may be as high as 20/80 in incomplete achromatopsia. Visual acuity is usually stable over time, but both nystagmus and sensitivity to bright light may improve slightly. The fundus is usually normal, but macular changes and vessel narrowing may be present in some individuals, and optical coherence tomography (OCT) reveals macular changes that can progress with time [<a class="bibr" href="#achm.REF.thomas.2012.1232" rid="achm.REF.thomas.2012.1232">Thomas et al 2012</a>].</p><p>Most individuals have <b>complete achromatopsia</b>, in which the symptoms can be explained by a total lack of function of all three types of cone (i.e., photopic) photoreceptors of the eye, with all visual functions being mediated by the rod (i.e., scotopic) photoreceptors.</p><p>Rarely, individuals have <b>incomplete achromatopsia</b>, in which one or more cone types may be partially functioning along with the rods. The symptoms are similar to those of individuals with complete achromatopsia but generally less severe [<a class="bibr" href="#achm.REF.sharpe.1999" rid="achm.REF.sharpe.1999">Sharpe et al 1999</a>]. Color discrimination ranges from well preserved to severely impaired; photophobia is usually absent; visual acuity is better preserved than in complete achromatopsia.</p></div><div id="achm.Phenotype_Correlations_by_Gene"><h3>Phenotype Correlations by Gene</h3><p><b>Complete achromatopsia.</b> The majority of individuals with biallelic pathogenic variants in <i>ATF6</i>, <i>CNGA3</i>, <i>CNGB3</i>, <i>GNAT2</i>, and <i>PDE6C</i> have complete achromatopsia with similar clinical features. A significant genotype-phenotype correlation cannot be observed; however, individuals with <i>ATF6</i>-associated achromatopsia usually have a poorly formed or absent foveal pit.</p><p>
|
|
<b>Incomplete achromatopsia</b>
|
|
</p><ul><li class="half_rhythm"><div>Certain <i>CNGA3</i> and <i>GNAT2</i> pathogenic variants are associated with a very mild phenotype of incomplete achromatopsia and oligo-cone trichromacy [<a class="bibr" href="#achm.REF.rosenberg.2004.4256" rid="achm.REF.rosenberg.2004.4256">Rosenberg et al 2004</a>, <a class="bibr" href="#achm.REF.vincent.2011.107" rid="achm.REF.vincent.2011.107">Vincent et al 2011</a>].</div></li><li class="half_rhythm"><div>Pathogenic variants in <i>PDE6H</i> lead to the incomplete form of achromatopsia [<a class="bibr" href="#achm.REF.kohl.2012.527" rid="achm.REF.kohl.2012.527">Kohl et al 2012</a>].</div></li><li class="half_rhythm"><div>Cone-rod dystrophy and macular dystrophy have been reported for pathogenic variants in <i>ATF6</i> [<a class="bibr" href="#achm.REF.carss.2017.75" rid="achm.REF.carss.2017.75">Carss et al 2017</a>, <a class="bibr" href="#achm.REF.skorczykwerner.2017.1210" rid="achm.REF.skorczykwerner.2017.1210">Skorczyk-Werner et al 2017</a>].</div></li></ul></div><div id="achm.Nomenclature"><h3>Nomenclature</h3><p>The <b>complete</b> form of achromatopsia is also referred to as rod monochromacy (monochromatism), complete (or total) color blindness (OMIM <a href="https://omim.org/entry/216900" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">216900</a>), day blindness (hemeralopia), or "Pingelapese blindness." Clinically, it is known as typical, complete achromatopsia or complete achromatopsia with reduced visual acuity.</p><p>The <b>incomplete</b> form of achromatopsia is also known clinically as atypical, incomplete achromatopsia or incomplete achromatopsia with reduced visual acuity.</p></div><div id="achm.Prevalence"><h3>Prevalence</h3><p>Achromatopsia is a rare disorder with an estimated prevalence of fewer than 1:30,000 [<a class="bibr" href="#achm.REF.sharpe.1999" rid="achm.REF.sharpe.1999">Sharpe et al 1999</a>].</p><p>Parental consanguinity is common in certain geographic regions. On the island of Pingelap in the eastern Caroline Islands in Micronesia, the prevalence of achromatopsia is between 4% and 10%, secondary to the founder variant <a href="/books/NBK1418/table/achm.T.cngb3_pathogenic_variants_discuss/?report=objectonly" target="object" rid-ob="figobachmTcngb3pathogenicvariantsdiscuss">p.Ser435Phe</a> in <i>CNGB3</i> [<a class="bibr" href="#achm.REF.sharpe.1999" rid="achm.REF.sharpe.1999">Sharpe et al 1999</a>].</p></div></div><div id="achm.Genetically_Related_Allelic_Disorde"><h2 id="_achm_Genetically_Related_Allelic_Disorde_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with biallelic pathogenic variants in <i>PDE6H</i>.</p><p>Allelic disorders observed in the other five achromatopsia-associated genes are discussed in <a href="/books/NBK1418/table/achm.T.allelic_disorders_to_consider_in/?report=objectonly" target="object" rid-ob="figobachmTallelicdisorderstoconsiderin">Tables 2a</a> and <a href="/books/NBK1418/table/achm.T.allelic_disorders_not_in_the_diff/?report=objectonly" target="object" rid-ob="figobachmTallelicdisordersnotinthediff">2b</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figachmTallelicdisorderstoconsiderin"><a href="/books/NBK1418/table/achm.T.allelic_disorders_to_consider_in/?report=objectonly" target="object" title="Table 2a. " class="img_link icnblk_img" rid-ob="figobachmTallelicdisorderstoconsiderin"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="achm.T.allelic_disorders_to_consider_in"><a href="/books/NBK1418/table/achm.T.allelic_disorders_to_consider_in/?report=objectonly" target="object" rid-ob="figobachmTallelicdisorderstoconsiderin">Table 2a. </a></h4><p class="float-caption no_bottom_margin">Allelic Disorders to Consider in the Differential Diagnosis of Achromatopsia </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figachmTallelicdisordersnotinthediff"><a href="/books/NBK1418/table/achm.T.allelic_disorders_not_in_the_diff/?report=objectonly" target="object" title="Table 2b. " class="img_link icnblk_img" rid-ob="figobachmTallelicdisordersnotinthediff"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="achm.T.allelic_disorders_not_in_the_diff"><a href="/books/NBK1418/table/achm.T.allelic_disorders_not_in_the_diff/?report=objectonly" target="object" rid-ob="figobachmTallelicdisordersnotinthediff">Table 2b. </a></h4><p class="float-caption no_bottom_margin">Allelic Disorders (Not in the Differential Diagnosis of Achromatopsia) </p></div></div></div><div id="achm.Differential_Diagnosis"><h2 id="_achm_Differential_Diagnosis_">Differential Diagnosis</h2><p>Achromatopsia is readily recognized by its characteristic features (see <a href="#achm.Suggestive_Findings">Suggestive Findings</a>). Conditions to consider in the differential diagnosis are congenital nystagmus (as nystagmus is usually one of the first manifestations) and cerebral achromatopsia or dyschromatopsia, which is associated with severe or total color vision deficits and can arise adventitiously after brain fever, cortical trauma, or cerebral infarction, especially involving lesions to the ventral occipital cortex [<a class="bibr" href="#achm.REF.bouvier.2006.183" rid="achm.REF.bouvier.2006.183">Bouvier & Engel 2006</a>].</p><p>Inherited retinal dystrophies that may be confused with achromatopsia are summarized in <a href="/books/NBK1418/table/achm.T.inherited_retinal_dystrophies_to/?report=objectonly" target="object" rid-ob="figobachmTinheritedretinaldystrophiesto">Table 3</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figachmTinheritedretinaldystrophiesto"><a href="/books/NBK1418/table/achm.T.inherited_retinal_dystrophies_to/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobachmTinheritedretinaldystrophiesto"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="achm.T.inherited_retinal_dystrophies_to"><a href="/books/NBK1418/table/achm.T.inherited_retinal_dystrophies_to/?report=objectonly" target="object" rid-ob="figobachmTinheritedretinaldystrophiesto">Table 3. </a></h4><p class="float-caption no_bottom_margin">Inherited Retinal Dystrophies to Consider in the Differential Diagnosis of Achromatopsia </p></div></div></div><div id="achm.Management"><h2 id="_achm_Management_">Management</h2><div id="achm.Evaluations_Following_Initial_Diagn"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with achromatopsia, the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended:</p><ul><li class="half_rhythm"><div>Standard clinical ophthalmologic evaluation and testing with attention to visual acuity and use of spectacles and/or contact lenses to achieve the best possible corrected visual acuity</div></li><li class="half_rhythm"><div>Color vision evaluation</div></li><li class="half_rhythm"><div>Consultation with a clinical geneticist and/or genetic counselor as treatment could be possible in the near future (See <a href="#achm.Therapies_Under_Investigation">Therapies Under Investigation</a>.)</div></li></ul></div><div id="achm.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Dark or special filter glasses or red-tinted contact lenses reduce photophobia and may improve visual acuity.</p><p>Low vision aids include high-powered magnifiers for reading as well as digital/electronic devices.</p><p>Children with achromatopsia should have preferential seating in the classroom (i.e., in the front to benefit maximally from magnifying devices and away from windows to reduce the effects of glare on vision).</p><p>Extensive information about learning and occupational aids is available from the Achromatopsia Network (<a href="http://www.achromat.info" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.achromat.info</a>).</p></div><div id="achm.Surveillance"><h3>Surveillance</h3><p>Ophthalmologic examination is indicated:</p><ul><li class="half_rhythm"><div>Every six to 12 months in children to monitor changes in refraction in order to achieve the best possible corrected visual acuity;</div></li><li class="half_rhythm"><div>Every two to three years in adults.</div></li></ul></div><div id="achm.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>To avoid additional light damage to the retina, it is recommended that individuals wear appropriate protective (dark) glasses in bright light.</p></div><div id="achm.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#achm.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="achm.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>In July 2012 a Phase I/II clinical trial (NCT01846052) investigating the therapeutic effects and safety of an intraocular implant releasing ciliary neurotrophic factor (CNTF) in individuals with <i>CNGB3</i>-related achromatopsia was started. No objectively measurable enhancement of cone function was found by assessments of visual acuity, mesopic increment sensitivity threshold, photopic electroretinogram, or color hue discrimination. Subjectively, individuals reported beneficial changes of visual function in the treated eyes, including reduced light sensitivity and aversion to bright light, but slowed adaptation to darkness, consistent with CNTF action on rod photoreceptors [<a class="bibr" href="#achm.REF.zein.2014.6301" rid="achm.REF.zein.2014.6301">Zein et al 2014</a>].</p><p>Several interventional Phase I/II clinical safety and efficacy trials for gene replacement therapy using viral AAV vectors for <i>CNGA3</i>-related achromatopsia (NCT02610582, NCT02935517) and <i>CNGB3</i>-related achromatopsia (NCT02599922, NCT03278873, NCT03001310) are currently running and recruiting patients.</p><p>In addition, clinical observational trials have been or are recruiting individuals for clinical assessment to establish the natural history of achromatopsia (NCT02435940, NCT01846052).</p><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for information on clinical studies for a wide range of diseases and conditions.</p></div></div><div id="achm.Genetic_Counseling"><h2 id="_achm_Genetic_Counseling_">Genetic Counseling</h2><p>
|
|
<i>Genetic counseling is the process of providing individuals and families with
|
|
information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
|
|
make informed medical and personal decisions. The following section deals with genetic
|
|
risk assessment and the use of family history and genetic testing to clarify genetic
|
|
status for family members; it is not meant to address all personal, cultural, or
|
|
ethical issues that may arise or to substitute for consultation with a genetics
|
|
professional</i>. —ED.</p><div id="achm.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Achromatopsia is inherited in an autosomal recessive manner.</p></div><div id="achm.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
|
|
<b>Parents of a proband</b>
|
|
</p><ul><li class="half_rhythm"><div>The parents of an affected child are obligate heterozygotes (i.e., carriers of one achromatopsia-related pathogenic variant).</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p>
|
|
<b>Sibs of a proband</b>
|
|
</p><ul><li class="half_rhythm"><div>At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p><b>Offspring of a proband.</b> The offspring of an individual with achromatopsia are obligate heterozygotes (carriers) for an achromatopsia-related pathogenic variant.</p><p><b>Other family members.</b> Each sib of the proband's parents is at a 50% risk of being a carrier of an achromatopsia-related pathogenic variant.</p></div><div id="achm.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the achromatopsia-related pathogenic variants in the family.</p></div><div id="achm.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>
|
|
<b>Family planning</b>
|
|
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.</div></li></ul></div><div id="achm.Prenatal_Testing_and_Preimplantatio"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the achromatopsia-related pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for achromatopsia are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="achm.Resources"><h2 id="_achm_Resources_">Resources</h2><p>
|
|
<i>GeneReviews staff has selected the following disease-specific and/or umbrella
|
|
support organizations and/or registries for the benefit of individuals with this disorder
|
|
and their families. GeneReviews is not responsible for the information provided by other
|
|
organizations. For information on selection criteria, click <a href="/books/n/gene/app4/?report=reader">here</a>.</i></p>
|
|
<ul><li class="half_rhythm"><div>
|
|
<b>Achroma Corp </b>
|
|
</div><div><b>Phone:</b> 724-841-4052</div><div><b>Email:</b> bvissari@achromacorp.org</div><div>
|
|
<a href="http://www.achromacorp.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.achromacorp.org</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>Achromatopsie Selbsthilfeverein e.V.</b>
|
|
</div><div>Germany</div><div><b>Email:</b> info@achromatopsie.org</div><div>
|
|
<a href="https://www.achromatopsie.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.achromatopsie.org</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>Associazione Acromati Italiani Onlus</b>
|
|
</div><div>Italy</div><div><b>Email:</b> info@acromatopsia.it</div><div>
|
|
<a href="http://www.acromatopsia.it/?page_id=213&lang=en" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.acromatopsia.it</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>National Eye Institute</b>
|
|
</div><div><b>Phone:</b> 301-496-5248</div><div><b>Email:</b> 2020@nei.nih.gov</div><div>
|
|
<a href="https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/low-vision" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Low Vision</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>National Library of Medicine Genetics Home Reference</b>
|
|
</div><div>
|
|
<a href="https://ghr.nlm.nih.gov/condition/colorvisiondeficiency" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Color vision deficiency</a>
|
|
</div></li></ul>
|
|
</div><div id="achm.Molecular_Genetics"><h2 id="_achm_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figachmmolgenTA"><a href="/books/NBK1418/table/achm.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobachmmolgenTA"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="achm.molgen.TA"><a href="/books/NBK1418/table/achm.molgen.TA/?report=objectonly" target="object" rid-ob="figobachmmolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">Achromatopsia: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figachmmolgenTB"><a href="/books/NBK1418/table/achm.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobachmmolgenTB"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="achm.molgen.TB"><a href="/books/NBK1418/table/achm.molgen.TB/?report=objectonly" target="object" rid-ob="figobachmmolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for Achromatopsia (View All in OMIM) </p></div></div><div id="achm.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>CNGB3</i>, <i>CNGA3</i>, <i>PDE6C</i>, <i>GNAT2</i>, and <i>PDE6H</i> are all expressed in the cone photoreceptor and are crucial for cone phototransduction:</p><ul><li class="half_rhythm"><div>Light-excited cone visual pigment molecules induce the exchange of GDP to GTP on the transducin alpha subunit (<b>GNAT2</b>) and its release from the inhibitory beta/gamma subunits.</div></li><li class="half_rhythm"><div>The activated GTP-transducin then binds and activates the alpha' subunit of the retinal cone photoreceptor phosphodiesterase (<b>PDE6C</b>) by retracting the inhibitory gamma subunit (<b>PDE6H</b>).</div></li><li class="half_rhythm"><div>Retinal cone photoreceptor PDE6C hydrolyzes cGMP, reducing its intracellular concentration and causing closure of the heterotetrameric cGMP-gated cation channels (<b>CNGA3</b> and <b>CNGB3</b>) and, subsequently, membrane hyperpolarization [<a class="bibr" href="#achm.REF.lamb.2006.5137" rid="achm.REF.lamb.2006.5137">Lamb & Pugh 2006</a>].</div></li></ul><p>Transducin thus mediates the first step, the phosphodiesterase the intermediate, and the cGMP-gated channel represents the final step in the phototransduction cascade.</p><p>In contrast, the most recently identified ACHM-related gene, <i>ATF6</i>, encodes a ubiquitously expressed transmembrane transcription factor known for its function in the ATF6 unfolded protein response pathway [<a class="bibr" href="#achm.REF.walter.2011.1081" rid="achm.REF.walter.2011.1081">Walter & Ron 2011</a>, <a class="bibr" href="#achm.REF.wang.2012.857" rid="achm.REF.wang.2012.857">Wang & Kaufman 2012</a>, <a class="bibr" href="#achm.REF.kohl.2015.757" rid="achm.REF.kohl.2015.757">Kohl et al 2015</a>]. How and why pathogenic variants in this ubiquitously expressed gene result solely in cone dysfunction is to date unknown.</p><div id="achm.ATF6"><h4>
|
|
<i>ATF6</i>
|
|
</h4><p><b>Gene structure.</b>
|
|
<i>ATF</i> consists of 16 coding exons. For a detailed summary of gene and protein information, see <a href="/books/NBK1418/?report=reader#achm.molgen.TA">Table A</a>, <b>Gene</b>.</p><p><b>Pathogenic variants.</b> Thirteen different pathogenic variants have been reported in 15 families [<a class="bibr" href="#achm.REF.ansar.2015.941" rid="achm.REF.ansar.2015.941">Ansar et al 2015</a>, <a class="bibr" href="#achm.REF.kohl.2015.757" rid="achm.REF.kohl.2015.757">Kohl et al 2015</a>, <a class="bibr" href="#achm.REF.xu.2015.3889" rid="achm.REF.xu.2015.3889">Xu et al 2015</a>, <a class="bibr" href="#achm.REF.carss.2017.75" rid="achm.REF.carss.2017.75">Carss et al 2017</a>, <a class="bibr" href="#achm.REF.skorczykwerner.2017.1210" rid="achm.REF.skorczykwerner.2017.1210">Skorczyk-Werner et al 2017</a>]. Nine of the 13 are nonsense variants, splice site variants, small insertions, and deletions. Only four missense variants have been reported.</p><p>Six individuals (from 2 unrelated families of Irish/British descent) who are homozygous for c.970C>T have been identified; the families were shown to have a common haplotype of 0.7 Mb suggestive of a founder variant [<a class="bibr" href="#achm.REF.kohl.2015.757" rid="achm.REF.kohl.2015.757">Kohl et al 2015</a>]. Another pathogenic variant, <a href="/books/NBK1418/table/achm.T.atf6_pathogenic_variants_discusse/?report=objectonly" target="object" rid-ob="figobachmTatf6pathogenicvariantsdiscusse">c.1533+1G>C</a>, was observed recurrently in four French Canadian families, also suggesting a founder variant in this population [<a class="bibr" href="#achm.REF.kohl.2015.757" rid="achm.REF.kohl.2015.757">Kohl et al 2015</a>, <a class="bibr" href="#achm.REF.xu.2015.3889" rid="achm.REF.xu.2015.3889">Xu et al 2015</a>].</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figachmTatf6pathogenicvariantsdiscusse"><a href="/books/NBK1418/table/achm.T.atf6_pathogenic_variants_discusse/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobachmTatf6pathogenicvariantsdiscusse"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="achm.T.atf6_pathogenic_variants_discusse"><a href="/books/NBK1418/table/achm.T.atf6_pathogenic_variants_discusse/?report=objectonly" target="object" rid-ob="figobachmTatf6pathogenicvariantsdiscusse">Table 4. </a></h4><p class="float-caption no_bottom_margin"><i>ATF6</i> Pathogenic Variants Discussed in This <i>GeneReview</i> </p></div></div><p><b>Normal gene product.</b>
|
|
<i>ATF6</i> encodes a 670-amino-acid, ubiquitously expressed 90-kd ER stress-regulated transmembrane transcription factor known for its function in one of three unfolded protein response pathways (i.e., ATF6 pathway). It is required for ER stress response and transcriptional induction from ER stress-response elements (ERSEs). On induction of ER stress, the cytosolic ~400-residue N-terminal portion of ATF6 (N-ATF6) is released. N-ATF6 possesses the transcriptional activation domain, the bZIP domain, the DNA-binding domain, and nuclear localization signals. It translocates to the nucleus, where it interacts with several other proteins to form an ERSE-binding complex that is responsible for the induction of ER stress genes (ERSGs) [<a class="bibr" href="#achm.REF.walter.2011.1081" rid="achm.REF.walter.2011.1081">Walter & Ron 2011</a>, <a class="bibr" href="#achm.REF.wang.2012.857" rid="achm.REF.wang.2012.857">Wang & Kaufman 2012</a>].</p><p><b>Abnormal gene product.</b> Most pathogenic missense variants result in loss of protein function. One missense variant, <a href="/books/NBK1418/table/achm.T.atf6_pathogenic_variants_discusse/?report=objectonly" target="object" rid-ob="figobachmTatf6pathogenicvariantsdiscusse">p.Arg324Cys</a>, localizes to the basic region of the bZIP domain, affecting an arginine residue that is conserved not only among transcription factors of the ATF family but also in those of the AP-1 family, severely impairing ATF6 transcriptional activity [<a class="bibr" href="#achm.REF.kohl.2015.757" rid="achm.REF.kohl.2015.757">Kohl et al 2015</a>]. The <a href="/books/NBK1418/table/achm.T.atf6_pathogenic_variants_discusse/?report=objectonly" target="object" rid-ob="figobachmTatf6pathogenicvariantsdiscusse">p.Arg324Cys</a> variant was functionally characterized in detail and shown to impair transcriptional activity [<a class="bibr" href="#achm.REF.kohl.2015.757" rid="achm.REF.kohl.2015.757">Kohl et al 2015</a>, <a class="bibr" href="#achm.REF.chiang.2017.400" rid="achm.REF.chiang.2017.400">Chiang et al 2017</a>].</p><p>Other missense changes have been studied and divided into class I, 2, or 3:</p><ul><li class="half_rhythm"><div>Class 1. Disease-associated <i>ATF6</i> missense variants that result in impaired ER-to-Golgi trafficking and diminished regulated intramembrane proteolysis and transcriptional activity</div></li><li class="half_rhythm"><div>Class 2. Disease-associated <i>ATF6</i> missense variants that retain the entire ATF6 cytosolic domain with fully intact transcriptional activity and constitutive induction of downstream target genes, even in the absence of ER stress</div></li><li class="half_rhythm"><div>Class 3. ATF6 missense variants with complete loss of transcriptional activity because of absent or defective bZIP domains</div></li></ul><p>Primary fibroblasts from patients with class 1 or class 3 <i>ATF6</i> pathogenic variants show increased cell death in response to ER stress [<a class="bibr" href="#achm.REF.chiang.2017.400" rid="achm.REF.chiang.2017.400">Chiang et al 2017</a>].</p><p>Of note, the <i>Atf6</i> knockout mouse model does not recapitulate the human achromatopsia phenotype [<a class="bibr" href="#achm.REF.kohl.2015.757" rid="achm.REF.kohl.2015.757">Kohl et al 2015</a>].</p></div><div id="achm.CNGA3"><h4>
|
|
<i>CNGA3</i>
|
|
</h4><p><b>Gene structure.</b>
|
|
<i>CNGA3</i> consists of eight coding exons [<a class="bibr" href="#achm.REF.wissinger.2001.722" rid="achm.REF.wissinger.2001.722">Wissinger et al 2001</a>]. For a detailed summary of gene and protein information, see <a href="/books/NBK1418/?report=reader#achm.molgen.TA">Table A</a>, <b>Gene</b>.</p><p><b>Pathogenic variants.</b> More than 150 different pathogenic variants have been associated with ACHM [<a class="bibr" href="#achm.REF.kohl.1998.257" rid="achm.REF.kohl.1998.257">Kohl et al 1998</a>, <a class="bibr" href="#achm.REF.wissinger.2001.722" rid="achm.REF.wissinger.2001.722">Wissinger et al 2001</a>, <a class="bibr" href="#achm.REF.johnson.2004.e20" rid="achm.REF.johnson.2004.e20">Johnson et al 2004</a>, <a class="bibr" href="#achm.REF.tr_nkner.2004.138" rid="achm.REF.tr_nkner.2004.138">Tränkner et al 2004</a>, <a class="bibr" href="#achm.REF.nishiguchi.2005.248" rid="achm.REF.nishiguchi.2005.248">Nishiguchi et al 2005</a>, <a class="bibr" href="#achm.REF.vars_nyi.2005.996" rid="achm.REF.vars_nyi.2005.996">Varsányi et al 2005</a>, <a class="bibr" href="#achm.REF.ahuja.2008.1293" rid="achm.REF.ahuja.2008.1293">Ahuja et al 2008</a>, <a class="bibr" href="#achm.REF.koeppen.2008.2391" rid="achm.REF.koeppen.2008.2391">Koeppen et al 2008</a>, <a class="bibr" href="#achm.REF.reuter.2008.1228" rid="achm.REF.reuter.2008.1228">Reuter et al 2008</a>, <a class="bibr" href="#achm.REF.koeppen.2010.830" rid="achm.REF.koeppen.2010.830">Koeppen et al 2010</a>, <a class="bibr" href="#achm.REF.thiadens.2010.825" rid="achm.REF.thiadens.2010.825">Thiadens et al 2010</a>, <a class="bibr" href="#achm.REF.genead.2011.7298" rid="achm.REF.genead.2011.7298">Genead et al 2011</a>, <a class="bibr" href="#achm.REF.vincent.2011.107" rid="achm.REF.vincent.2011.107">Vincent et al 2011</a>]. The vast majority of pathogenic variants are missense (~80%). Only a few nonsense variants, insertions, and deletions have been observed.</p><p><b>Normal gene product.</b>
|
|
<i>CNGA3</i> encodes the cyclic nucleotide-gated cation channel alpha 3 (the alpha subunit of the cone photoreceptor cGMP-gated cation channel [CNG]). CNGA3 has 694 amino acids and a predicted weight of 78.8 kd. An alternatively spliced exon that extends the open reading frame by an additional 55 amino acids has been reported [<a class="bibr" href="#achm.REF.wissinger.2001.722" rid="achm.REF.wissinger.2001.722">Wissinger et al 2001</a>]. Alpha subunits on CNG channels are able to form functional homo-oligomeric channels, yet their biophysical properties differ from those of heteromeric native CNG channels consisting of three alpha subunits and one beta subunit.</p><p><b>Abnormal gene product.</b> Functional analysis has shown that in many cases channel function is strongly impaired or completely absent. The pathogenic missense variants mostly affect amino acid residues that are highly conserved among the members of the CNG channel family, and cluster at structural and functional domains including the cGMP-binding domain [<a class="bibr" href="#achm.REF.wissinger.2001.722" rid="achm.REF.wissinger.2001.722">Wissinger et al 2001</a>, <a class="bibr" href="#achm.REF.faillace.2004.22643" rid="achm.REF.faillace.2004.22643">Faillace et al 2004</a>, <a class="bibr" href="#achm.REF.patel.2005.2282" rid="achm.REF.patel.2005.2282">Patel et al 2005</a>, <a class="bibr" href="#achm.REF.koeppen.2008.2391" rid="achm.REF.koeppen.2008.2391">Koeppen et al 2008</a>, <a class="bibr" href="#achm.REF.reuter.2008.1228" rid="achm.REF.reuter.2008.1228">Reuter et al 2008</a>].</p><p>Some pathogenic variants in the pore region and the cGMP binding domain are associated with incomplete achromatopsia. These abnormal proteins can form functional channels, but with grossly altered properties, including altered affinity for cGMP and/or cAMP, and changes in the gating properties of the cone CNG channels, like Ca<sup>2+</sup> blockage and permeation [<a class="bibr" href="#achm.REF.tr_nkner.2004.138" rid="achm.REF.tr_nkner.2004.138">Tränkner et al 2004</a>, <a class="bibr" href="#achm.REF.liu.2005.c187" rid="achm.REF.liu.2005.c187">Liu & Varnum 2005</a>, <a class="bibr" href="#achm.REF.reuter.2008.1228" rid="achm.REF.reuter.2008.1228">Reuter et al 2008</a>, <a class="bibr" href="#achm.REF.koeppen.2010.830" rid="achm.REF.koeppen.2010.830">Koeppen et al 2010</a>].</p><p>Animal models have helped to clarify the underlying pathogenic mechanisms:</p><ul><li class="half_rhythm"><div><b>Mouse.</b>
|
|
<i>Cnga3<sup>(-/-)</sup></i> mice show absence of cone function, a decrease in the number of cones in the retina, and morphologic abnormalities of the remaining cones. <i>Cnga3</i><sup>(-/-)</sup> cones fail to transport opsin into the outer segment and downregulate various proteins of the phototransduction cascade. Apoptotic cell death is induced; however, loss of <i>Cnga3</i> does not appear to affect the transcription of other cone-specific genes [<a class="bibr" href="#achm.REF.biel.1999.7553" rid="achm.REF.biel.1999.7553">Biel et al 1999</a>, <a class="bibr" href="#achm.REF.michalakis.2005.1516" rid="achm.REF.michalakis.2005.1516">Michalakis et al 2005</a>]. Gene therapy has been successfully tested in these mouse models and shown to restore cone-mediated vision [<a class="bibr" href="#achm.REF.michalakis.2012.183" rid="achm.REF.michalakis.2012.183">Michalakis et al 2012</a>].</div></li><li class="half_rhythm"><div><b>Sheep.</b> Lambs with congenital day blindness are homozygous for the pathogenic nonsense variant <a href="https://www.ncbi.nlm.nih.gov/nuccore/FN377574" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">FN377574</a>:c.706C>T (p.Arg236Ter) in the ovine <i>CNGA3</i> and serve as animal models for studying human achromatopsia and evaluating gene therapeutic approaches [<a class="bibr" href="#achm.REF.reicher.2010.101" rid="achm.REF.reicher.2010.101">Reicher et al 2010</a>, <a class="bibr" href="#achm.REF.banin.2015.1423" rid="achm.REF.banin.2015.1423">Banin et al 2015</a>].</div></li></ul></div><div id="achm.CNGB3"><h4>
|
|
<i>CNGB3</i>
|
|
</h4><p><b>Gene structure.</b>
|
|
<i>CNGB3</i> consists of 18 coding exons [<a class="bibr" href="#achm.REF.kohl.2000.2107" rid="achm.REF.kohl.2000.2107">Kohl et al 2000</a>]. For a detailed summary of gene and protein information, see <a href="/books/NBK1418/?report=reader#achm.molgen.TA">Table A</a>, <b>Gene</b>.</p><p><b>Pathogenic variants.</b> More than 125 different pathogenic variants have been reported [<a class="bibr" href="#achm.REF.kohl.2000.2107" rid="achm.REF.kohl.2000.2107">Kohl et al 2000</a>, <a class="bibr" href="#achm.REF.sundin.2000.289" rid="achm.REF.sundin.2000.289">Sundin et al 2000</a>, <a class="bibr" href="#achm.REF.rojas.2002.638" rid="achm.REF.rojas.2002.638">Rojas et al 2002</a>, <a class="bibr" href="#achm.REF.johnson.2004.e20" rid="achm.REF.johnson.2004.e20">Johnson et al 2004</a>, <a class="bibr" href="#achm.REF.michaelides.2004.1975" rid="achm.REF.michaelides.2004.1975">Michaelides et al 2004</a>, <a class="bibr" href="#achm.REF.okada.2004.2324" rid="achm.REF.okada.2004.2324">Okada et al 2004</a>, <a class="bibr" href="#achm.REF.kohl.2005.302" rid="achm.REF.kohl.2005.302">Kohl et al 2005</a>, <a class="bibr" href="#achm.REF.nishiguchi.2005.248" rid="achm.REF.nishiguchi.2005.248">Nishiguchi et al 2005</a>, <a class="bibr" href="#achm.REF.vars_nyi.2005.996" rid="achm.REF.vars_nyi.2005.996">Varsányi et al 2005</a>, <a class="bibr" href="#achm.REF.khan.2007.3864" rid="achm.REF.khan.2007.3864">Khan et al 2007</a>, <a class="bibr" href="#achm.REF.wiszniewski.2007.433" rid="achm.REF.wiszniewski.2007.433">Wiszniewski et al 2007</a>, <a class="bibr" href="#achm.REF.thiadens.2009b.1984" rid="achm.REF.thiadens.2009b.1984">Thiadens et al 2009b</a>, <a class="bibr" href="#achm.REF.azam.2010.774" rid="achm.REF.azam.2010.774">Azam et al 2010</a>, <a class="bibr" href="#achm.REF.mayer.2017.1579" rid="achm.REF.mayer.2017.1579">Mayer et al 2017</a>]. The vast majority are pathogenic nonsense variants, frameshift deletions and insertions, and putative splice site variants. Only a few pathogenic missense variants (~10%) have been observed.</p><p>One, resulting in the p.Ser435Phe mutated protein, causes "Pingelapese blindness" in achromats originating from the island of Pingelap in Micronesia [<a class="bibr" href="#achm.REF.kohl.2000.2107" rid="achm.REF.kohl.2000.2107">Kohl et al 2000</a>, <a class="bibr" href="#achm.REF.sundin.2000.289" rid="achm.REF.sundin.2000.289">Sundin et al 2000</a>].</p><p>The recurrent single base-pair deletion <a href="/books/NBK1418/table/achm.T.cngb3_pathogenic_variants_discuss/?report=objectonly" target="object" rid-ob="figobachmTcngb3pathogenicvariantsdiscuss">c.1148delC</a> is the most common pathogenic variant underlying achromatopsia worldwide, accounting for approximately 70% of all <i>CNGB3</i> disease-causing alleles and approximately 40% of all achromatopsia-associated alleles. The c.1148delC deletion results from a founder effect [<a class="bibr" href="#achm.REF.wiszniewski.2007.433" rid="achm.REF.wiszniewski.2007.433">Wiszniewski et al 2007</a>].</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figachmTcngb3pathogenicvariantsdiscuss"><a href="/books/NBK1418/table/achm.T.cngb3_pathogenic_variants_discuss/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobachmTcngb3pathogenicvariantsdiscuss"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="achm.T.cngb3_pathogenic_variants_discuss"><a href="/books/NBK1418/table/achm.T.cngb3_pathogenic_variants_discuss/?report=objectonly" target="object" rid-ob="figobachmTcngb3pathogenicvariantsdiscuss">Table 5. </a></h4><p class="float-caption no_bottom_margin"><i>CNGB3</i> Pathogenic Variants Discussed in This <i>GeneReview</i> </p></div></div><p><b>Normal gene product.</b>
|
|
<i>CNGB3</i> encodes for cyclic nucleotide-gated cation channel beta 3 (the beta subunit of the cone photoreceptor cGMP-gated cation channel). CNGB3 is 809 amino acids long. The beta subunits are not able to form functional homo-oligomeric channels; they are therefore thought to be modulatory subunits. Functional cone CNG channels consist of three alpha subunits and one beta subunit.</p><p><b>Abnormal gene product.</b> Functional analysis has shown that in many cases channel function is strongly impaired or completely absent [<a class="bibr" href="#achm.REF.peng.2003.34533" rid="achm.REF.peng.2003.34533">Peng et al 2003</a>, <a class="bibr" href="#achm.REF.okada.2004.2324" rid="achm.REF.okada.2004.2324">Okada et al 2004</a>, <a class="bibr" href="#achm.REF.bright.2005.1141" rid="achm.REF.bright.2005.1141">Bright et al 2005</a>]. However, certain disease-associated <i>CNGB3</i> variants in the subunit are apparent gain-of-function variants [<a class="bibr" href="#achm.REF.okada.2004.2324" rid="achm.REF.okada.2004.2324">Okada et al 2004</a>, <a class="bibr" href="#achm.REF.bright.2005.1141" rid="achm.REF.bright.2005.1141">Bright et al 2005</a>]. Expression of human wild type <i>CNGA3</i> and mutated <i>CNGB3</i> containing the Pingelapese blindness-associated <a href="/books/NBK1418/table/achm.T.cngb3_pathogenic_variants_discuss/?report=objectonly" target="object" rid-ob="figobachmTcngb3pathogenicvariantsdiscuss">p.Ser435Phe</a> variant generated functional heteromeric channels that exhibited an increase in apparent affinity for both cAMP and cGMP and changes in the pore properties of the channel compared with wild type heteromeric channels.</p><p>Animal models have helped to clarify the underlying pathogenic mechanisms. Two naturally occurring <i>CNGB3-</i>null canine models, Alaskan malamute and German shorthaired pointer, have been identified [<a class="bibr" href="#achm.REF.sidjanin.2002.1823" rid="achm.REF.sidjanin.2002.1823">Sidjanin et al 2002</a>]. In the Alaskan malamute, cone-degenerate pups develop day blindness and photophobia. Cone function, detectable on electroretinogram in very young affected pups, begins to fail at a few weeks' age and is undetectable in mature affected dogs. Adult affected retinas lack all cones. The first gene therapy studies in these animals showed restoration of cone-mediated vision, but the success was dependent on the age of intervention [<a class="bibr" href="#achm.REF.kom_romy.2010.2581" rid="achm.REF.kom_romy.2010.2581">Komáromy et al 2010</a>].</p></div><div id="achm.GNAT2"><h4>
|
|
<i>GNAT2</i>
|
|
</h4><p><b>Gene structure.</b>
|
|
<i>GNAT2</i> consists of eight coding exons. For a detailed summary of gene and protein information, see <a href="/books/NBK1418/?report=reader#achm.molgen.TA">Table A</a>, <b>Gene</b>.</p><p><b>Pathogenic variants.</b> Sixteen different disease-associated variants (nonsense variant, deletions and/or insertions, one large deletion of exon 4, and a variant <a href="/books/NBK1418/table/achm.T.gnat2_pathogenic_variants_discuss/?report=objectonly" target="object" rid-ob="figobachmTgnat2pathogenicvariantsdiscuss">c.461+24G>A</a> activating a cryptic splice site and resulting in frameshift and PTC) have been described to date [<a class="bibr" href="#achm.REF.aligianis.2002.656" rid="achm.REF.aligianis.2002.656">Aligianis et al 2002</a>, <a class="bibr" href="#achm.REF.kohl.2002.422" rid="achm.REF.kohl.2002.422">Kohl et al 2002</a>, <a class="bibr" href="#achm.REF.michaelides.2003.1317" rid="achm.REF.michaelides.2003.1317">Michaelides et al 2003</a>, <a class="bibr" href="#achm.REF.pi_a.2004.265" rid="achm.REF.pi_a.2004.265">Piña et al 2004</a>, <a class="bibr" href="#achm.REF.rosenberg.2004.4256" rid="achm.REF.rosenberg.2004.4256">Rosenberg et al 2004</a>, <a class="bibr" href="#achm.REF.ouechtati.2011.22" rid="achm.REF.ouechtati.2011.22">Ouechtati et al 2011</a>, <a class="bibr" href="#achm.REF.langlo.2016.3984" rid="achm.REF.langlo.2016.3984">Langlo et al 2016</a>, <a class="bibr" href="#achm.REF.bryant.2017.49" rid="achm.REF.bryant.2017.49">Bryant et al 2017</a>, <a class="bibr" href="#achm.REF.carss.2017.75" rid="achm.REF.carss.2017.75">Carss et al 2017</a>, <a class="bibr" href="#achm.REF.taylor.2017.985" rid="achm.REF.taylor.2017.985">Taylor et al 2017</a>, <a class="bibr" href="#achm.REF.ueno.2017.92" rid="achm.REF.ueno.2017.92">Ueno et al 2017</a>].</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figachmTgnat2pathogenicvariantsdiscuss"><a href="/books/NBK1418/table/achm.T.gnat2_pathogenic_variants_discuss/?report=objectonly" target="object" title="Table 6. " class="img_link icnblk_img" rid-ob="figobachmTgnat2pathogenicvariantsdiscuss"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="achm.T.gnat2_pathogenic_variants_discuss"><a href="/books/NBK1418/table/achm.T.gnat2_pathogenic_variants_discuss/?report=objectonly" target="object" rid-ob="figobachmTgnat2pathogenicvariantsdiscuss">Table 6. </a></h4><p class="float-caption no_bottom_margin"><i>GNAT2</i> Pathogenic Variants Discussed in This <i>GeneReview</i> </p></div></div><p><b>Normal gene product.</b>
|
|
<i>GNAT2</i> encodes for guanine nucleotide-binding protein G(t), alpha-2 subunit (the cone-specific alpha subunit of transducin), a heterotrimeric G protein that couples to the cone photopigments. The protein is 354 amino acids long.</p><p><b>Abnormal gene product.</b> The majority of pathogenic variants result in loss of protein function [<a class="bibr" href="#achm.REF.cai.2001.4877" rid="achm.REF.cai.2001.4877">Cai et al 2001</a>]. The c.461+24G>A variant results in leaky aberrant splicing, resulting in a milder phenotype described as incomplete achromatopsia or oligo-cone trichromacy [<a class="bibr" href="#achm.REF.rosenberg.2004.4256" rid="achm.REF.rosenberg.2004.4256">Rosenberg et al 2004</a>].</p><p>Animal models have helped to clarify the underlying pathogenic mechanisms.</p><p>An achromatopsia mouse model is homozygous for the murine <i>Gnat2</i> pathogenic variant <a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_008141.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_008141.3</a>:c.598G>A (p.Asp200Asn) in exon 6 (also referred to as the <i>cpfl3</i> variant<i>)</i> [<a class="bibr" href="#achm.REF.chang.2006.5017" rid="achm.REF.chang.2006.5017">Chang et al 2006</a>]. Homozygous mice have poor cone-mediated responses on electroretinogram (ERG) at three weeks that become undetectable by nine months. Microscopy of the retina reveals progressive vacuolization of the photoreceptor outer segments. Immunocytochemistry with cone-specific markers shows progressive loss of labeling for Gnat2 protein, but the cone outer segments in the oldest mice examined remain intact [<a class="bibr" href="#achm.REF.chang.2006.5017" rid="achm.REF.chang.2006.5017">Chang et al 2006</a>].</p></div><div id="achm.PDE6C"><h4>
|
|
<i>PDE6C</i>
|
|
</h4><p><b>Gene structure.</b>
|
|
<i>PDE6C</i> consists of 22 coding exons [<a class="bibr" href="#achm.REF.piriev.1995.429" rid="achm.REF.piriev.1995.429">Piriev et al 1995</a>]. For a detailed summary of gene and protein information, see <a href="/books/NBK1418/?report=reader#achm.molgen.TA">Table A</a>, <b>Gene</b>.</p><p><b>Pathogenic variants.</b> More than 50 different pathogenic variants in <i>PDE6C</i> have been described; they include missense variants, nonsense variants, small indels, and variants affecting splicing [<a class="bibr" href="#achm.REF.chang.2009.19581" rid="achm.REF.chang.2009.19581">Chang et al 2009</a>, <a class="bibr" href="#achm.REF.thiadens.2009b.1984" rid="achm.REF.thiadens.2009b.1984">Thiadens et al 2009b</a>, <a class="bibr" href="#achm.REF.grau.2011.719" rid="achm.REF.grau.2011.719">Grau et al 2011</a>, <a class="bibr" href="#achm.REF.huang.2013.e65546" rid="achm.REF.huang.2013.e65546">Huang et al 2013</a>, <a class="bibr" href="#achm.REF.weisschuh.2018.1366" rid="achm.REF.weisschuh.2018.1366">Weisschuh et al 2018</a>].</p><p><b>Normal gene product.</b>
|
|
<i>PDE6C</i> encodes PDE6C, the phosphodiesterase 6C, cGMP-specific, cone, alpha-prime. This alpha' subunit of the cone-specific phosphodiesterase consists of 858 amino acids.</p><p><b>Abnormal gene product.</b> Disease-associated variants result in markedly reduced to completely absent PDE6C enzymatic activity [<a class="bibr" href="#achm.REF.chang.2009.19581" rid="achm.REF.chang.2009.19581">Chang et al 2009</a>, <a class="bibr" href="#achm.REF.grau.2011.719" rid="achm.REF.grau.2011.719">Grau et al 2011</a>].</p><p>Animal models have helped to clarify the underlying pathogenic mechanisms. The cone photoreceptor function loss 1 (<i>cpfl1</i>) mouse mutant is a model for <i>Pde6c-</i>related achromatopsia [<a class="bibr" href="#achm.REF.chang.2009.19581" rid="achm.REF.chang.2009.19581">Chang et al 2009</a>], which has a 116-bp insertion between exons 4 and 5 (<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001170959.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_001170959.1</a>:c.864_865ins116) and an additional 1-bp deletion in exon 7 (<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001170959.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_001170959.1</a>:c.1042delT) in <i>cis</i> (on the same allele). The phenotype can be easily typed by ERG as early as age three weeks. Histology of <i>cpfl1</i> mouse retinae revealed grossly normal morphology and layering. However, as early as age three weeks, there was vacuolization of a small subset of cells in the photoreceptor layer with subsequent rapid, progressive depletion of cone photoreceptors. Loss of cones progresses, such that very few were detected in retinal sections of five-month-old animals [<a class="bibr" href="#achm.REF.chang.2009.19581" rid="achm.REF.chang.2009.19581">Chang et al 2009</a>].</p></div><div id="achm.PDE6H"><h4>
|
|
<i>PDE6H</i>
|
|
</h4><p><b>Gene structure.</b>
|
|
<i>PDE6H</i> consists of only three coding exons [<a class="bibr" href="#achm.REF.shimizumatsumoto.1996.121" rid="achm.REF.shimizumatsumoto.1996.121">Shimizu-Matsumoto et al 1996</a>]. For a detailed summary of gene and protein information, see <a href="/books/NBK1418/?report=reader#achm.molgen.TA">Table A</a>, <b>Gene</b>.</p><p><b>Pathogenic variants.</b> Originally the single homozygous pathogenic nonsense variant <a href="/books/NBK1418/table/achm.T.gnat2_pathogenic_variants_discuss/?report=objectonly" target="object" rid-ob="figobachmTgnat2pathogenicvariantsdiscuss">c.35C>G</a> in <i>PDE6H</i> was described in three affected individuals from two independent families originating from Belgium and the Netherlands [<a class="bibr" href="#achm.REF.kohl.2012.527" rid="achm.REF.kohl.2012.527">Kohl et al 2012</a>]. Recently, two Pakistani brothers were shown to be homozygous for the same pathogenic variant [<a class="bibr" href="#achm.REF.pedurupillay.2016.e41" rid="achm.REF.pedurupillay.2016.e41">Pedurupillay et al 2016</a>].</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figachmTpde6hpathogenicvariantsdiscuss"><a href="/books/NBK1418/table/achm.T.pde6h_pathogenic_variants_discuss/?report=objectonly" target="object" title="Table 7. " class="img_link icnblk_img" rid-ob="figobachmTpde6hpathogenicvariantsdiscuss"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="achm.T.pde6h_pathogenic_variants_discuss"><a href="/books/NBK1418/table/achm.T.pde6h_pathogenic_variants_discuss/?report=objectonly" target="object" rid-ob="figobachmTpde6hpathogenicvariantsdiscuss">Table 7. </a></h4><p class="float-caption no_bottom_margin"><i>PDE6H</i> Pathogenic Variants Discussed in This <i>GeneReview</i> </p></div></div><p><b>Normal gene product.</b>
|
|
<i>PDE6H</i> encodes phosphodiesterase 6H, cGMP-specific, cone, gamma; PDE6H, the inhibitory gamma subunit of the cone photoreceptor phosphodiesterase. PDE6H consists of only 83 amino acids.</p><p><b>Abnormal gene production.</b> The sole <i>PDE6H</i> nonsense variant is predicted to result in complete loss of function of PDE6H either by degradation of the mRNA by nonsense-mediated decay or the truncation of the protein [<a class="bibr" href="#achm.REF.kohl.2012.527" rid="achm.REF.kohl.2012.527">Kohl et al 2012</a>].</p><p>Of note, the <i>Pde6h</i> knockout mouse model does not recapitulate the human achromatopsia phenotype [<a class="bibr" href="#achm.REF.brennenstuhl.2015.10242" rid="achm.REF.brennenstuhl.2015.10242">Brennenstuhl et al 2015</a>].</p></div></div></div><div id="achm.Chapter_Notes"><h2 id="_achm_Chapter_Notes_">Chapter Notes</h2><div id="achm.Author_History"><h3>Author History</h3><p>Herbert Jägle, MD, FEBO, Dhabil Prof (2004-present)<br />Susanne Kohl, Bsc, MSc, PhD (2004-present)<br />Lindsay T Sharpe, BA (Hons), MA, PhD, Dhabil (med); Institute of Ophthalmology, UK (2004-2013)<br />Ditta Zobor, MD, PhD, FEBO, Dhabil (2018-present)<br />Bernd Wissinger, BSc, MSc, PhD, Prof (2004-present)</p></div><div id="achm.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>20 September 2018 (bp) Comprehensive update posted live</div></li><li class="half_rhythm"><div>25 February 2016 (sk) Revision: Therapies Under Investigation</div></li><li class="half_rhythm"><div>29 October 2015 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>27 June 2013 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>23 December 2010 (cd) Revision: sequence analysis available clinically for mutations in <i>GNAT2</i></div></li><li class="half_rhythm"><div>23 September 2010 (cd) Revision: prenatal testing available for achromatopsia 2 and 3; achromatopsia 5 (caused by mutations in <i>PDE6C</i>) added; clinical testing and prenatal testing available for <i>PDE6C</i> mutations.</div></li><li class="half_rhythm"><div>25 June 2009 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>23 October 2006 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>24 June 2004 (me) Review posted live</div></li><li class="half_rhythm"><div>17 February 2004 (sk, bw) Original submission</div></li></ul></div></div><div id="achm.References"><h2 id="_achm_References_">References</h2><div id="achm.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.aboshiha.2014.6340">Aboshiha
|
|
J, Luong
|
|
V, Cowing
|
|
J, Dubis
|
|
AM, Bainbridge
|
|
JW, Ali
|
|
RR, Webster
|
|
AR, Moore
|
|
AT, Fitzke
|
|
FW, Michaelides
|
|
M. Dark-adaptation functions in molecularly confirmed achromatopsia and the implications for assessment in retinal therapy trials.
|
|
Invest Ophthalmol Vis Sci.
|
|
2014;55:6340–9.
|
|
[<a href="/pmc/articles/PMC4193759/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4193759</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25168900" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25168900</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.ahuja.2008.1293">Ahuja
|
|
Y, Kohl
|
|
S, Traboulsi
|
|
EI. CNGA3 mutations in two United Arab Emirates families with achromatopsia.
|
|
Mol Vis.
|
|
2008;14:1293–7.
|
|
[<a href="/pmc/articles/PMC2464613/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2464613</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18636117" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18636117</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.aligianis.2002.656">Aligianis
|
|
IA, Forshew
|
|
T, Johnson
|
|
S, Michaelides
|
|
M, Johnson
|
|
CA, Trembath
|
|
RC, Hunt
|
|
DM, Moore
|
|
AT, Maher
|
|
ER. Mapping of a novel locus for achromatopsia (ACHM4) to 1p and identification of a germline mutation in the alpha subunit of cone transducin (GNAT2).
|
|
J Med Genet.
|
|
2002;39:656–60.
|
|
[<a href="/pmc/articles/PMC1735242/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1735242</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/12205108" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12205108</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.ansar.2015.941">Ansar
|
|
M, Santos-Cortez
|
|
RL, Saqib
|
|
MA, Zulfiqar
|
|
F, Lee
|
|
K, Ashraf
|
|
NM, Ullah
|
|
E, Wang
|
|
X, Sajid
|
|
S, Khan
|
|
FS, Amin-Ud-Din
|
|
M, Smith
|
|
JD, Shendure
|
|
J, Bamshad
|
|
MJ, Nickerson
|
|
DA, Hameed
|
|
A, Riazuddin
|
|
S, Ahmed
|
|
ZM, Ahmad
|
|
W, Leal
|
|
SM, et al.
|
|
Mutation of ATF6 causes autosomal recessive achromatopsia.
|
|
Hum Genet.
|
|
2015;134:941–50.
|
|
[<a href="/pmc/articles/PMC4529463/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4529463</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26063662" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26063662</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.azam.2010.774">Azam
|
|
M, Collin
|
|
RW, Shah
|
|
ST, Shah
|
|
AA, Khan
|
|
MI, Hussain
|
|
A, Sadeque
|
|
A, Strom
|
|
TM, Thiadens
|
|
AA, Roosing
|
|
S, den Hollander
|
|
AI, Cremers
|
|
FP, Qamar
|
|
R. Novel CNGA3 and CNGB3 mutations in two Pakistani families with achromatopsia.
|
|
Mol Vis.
|
|
2010;16:774–81.
|
|
[<a href="/pmc/articles/PMC2862243/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2862243</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20454696" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20454696</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.banin.2015.1423">Banin
|
|
E, Gootwine
|
|
E, Obolensky
|
|
A, Ezra-Elia
|
|
R, Ejzenberg
|
|
A, Zelinger
|
|
L, Honig
|
|
H, Rosov
|
|
A, Yamin
|
|
E, Sharon
|
|
D, Averbukh
|
|
E, Hauswirth
|
|
WW, Ofri
|
|
R. Gene augmentation therapy restores retinal function and visual behavior in a sheep model of CNGA3 achromatopsia.
|
|
Mol Ther.
|
|
2015;23:1423–33.
|
|
[<a href="/pmc/articles/PMC4817879/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4817879</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26087757" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26087757</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.biel.1999.7553">Biel
|
|
M, Seeliger
|
|
M, Pfeifer
|
|
A, Kohler
|
|
K, Gerstner
|
|
A, Ludwig
|
|
A, Jaissle
|
|
G, Fauser
|
|
S, Zrenner
|
|
E, Hofmann
|
|
F. Selective loss of cone function in mice lacking the cyclic nucleotide-gated channel CNG3.
|
|
Proc Natl Acad Sci U S A.
|
|
1999;96:7553–7.
|
|
[<a href="/pmc/articles/PMC22124/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC22124</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/10377453" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10377453</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.bijveld.2011.161">Bijveld
|
|
MM, Riemslag
|
|
FC, Kappers
|
|
AM, Hoeben
|
|
FP, van Genderen
|
|
MM. An extended 15 Hz ERG protocol (2): data of normal subjects and patients with achromatopsia, CSNB1, and CSNB2.
|
|
Doc Ophthalmol.
|
|
2011;123:161–72.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/21947599" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21947599</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.bouvier.2006.183">Bouvier
|
|
SE, Engel
|
|
SA. Behavioral deficits and cortical damage loci in cerebral achromatopsia.
|
|
Cereb Cortex.
|
|
2006;16:183–91.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15858161" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15858161</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.brennenstuhl.2015.10242">Brennenstuhl
|
|
C, Tanimoto
|
|
N, Burkard
|
|
M, Wagner
|
|
R, Bolz
|
|
S, Trifunovic
|
|
D, Kabagema-Bilan
|
|
C, Paquet-Durand
|
|
F, Beck
|
|
SC, Huber
|
|
G, Seeliger
|
|
MW, Ruth
|
|
P, Wissinger
|
|
B, Lukowski
|
|
R. Targeted ablation of the Pde6h gene in mice reveals cross-species differences in cone and rod phototransduction protein isoform inventory.
|
|
J Biol Chem.
|
|
2015;290:10242–55.
|
|
[<a href="/pmc/articles/PMC4400339/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4400339</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25739440" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25739440</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.bright.2005.1141">Bright
|
|
SR, Brown
|
|
TE, Varnum
|
|
MD. Disease-associated mutations in CNGB3 produce gain of function alterations in cone cyclic nucleotide-gated channels.
|
|
Mol Vis.
|
|
2005;11:1141–50.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/16379026" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16379026</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.bryant.2017.49">Bryant
|
|
L, Lozynska
|
|
O, Maguire
|
|
AM, Aleman
|
|
TS, Bennett
|
|
J. Prescreening whole exome sequencing results from patients with retinal degeneration for variants in genes associated with retinal degeneration.
|
|
Clin Ophthalmol.
|
|
2017;12:49–63.
|
|
[<a href="/pmc/articles/PMC5749571/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5749571</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29343940" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29343940</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.cai.2001.4877">Cai
|
|
K, Itoh
|
|
Y, Khorana
|
|
HG. Mapping of contact sites in complex formation between transducin and light-activated rhodopsin by covalent crosslinking: use of a photoactivatable reagent.
|
|
Proc Natl Acad Sci U S A.
|
|
2001;98:4877–82.
|
|
[<a href="/pmc/articles/PMC33131/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC33131</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/11320237" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11320237</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.carss.2017.75">Carss
|
|
KJ, Arno
|
|
G, Erwood
|
|
M, Stephens
|
|
J, Sanchis-Juan
|
|
A, Hull
|
|
S, Megy
|
|
K, Grozeva
|
|
D, Dewhurst
|
|
E, Malka
|
|
S, Plagnol
|
|
V, Penkett
|
|
C, Stirrups
|
|
K, Rizzo
|
|
R, Wright
|
|
G, Josifova
|
|
D, Bitner-Glindzicz
|
|
M, Scott
|
|
RH, Clement
|
|
E, Allen
|
|
L, Armstrong
|
|
R, Brady
|
|
AF, Carmichael
|
|
J, Chitre
|
|
M, Henderson
|
|
RHH, Hurst
|
|
J, MacLaren
|
|
RE, Murphy
|
|
E, Paterson
|
|
J, Rosser
|
|
E, Thompson
|
|
DA, Wakeling
|
|
E, Ouwehand
|
|
WH, Michaelides
|
|
M, Moore
|
|
AT, Webster
|
|
AR, Raymond
|
|
FL, et al.
|
|
Comprehensive rare variant analysis via whole-genome sequencing to determine the molecular pathology of inherited retinal disease.
|
|
Am J Hum Genet.
|
|
2017;100:75–90.
|
|
[<a href="/pmc/articles/PMC5223092/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5223092</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28041643" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28041643</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.chang.2006.5017">Chang
|
|
B, Dacey
|
|
MS, Hawes
|
|
NL, Hitchcock
|
|
PF, Milam
|
|
AH, Atmaca-Sonmez
|
|
P, Nusinowitz
|
|
S, Heckenlively
|
|
JR. Cone photoreceptor function loss-3, a novel mouse model of achromatopsia due to a mutation in Gnat2.
|
|
Invest Ophthalmol Vis Sci.
|
|
2006;47:5017–21.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/17065522" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17065522</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.chang.2009.19581">Chang
|
|
B, Grau
|
|
T, Dangel
|
|
S, Hurd
|
|
R, Jurklies
|
|
B, Sener
|
|
EC, Andreasson
|
|
S, Dollfus
|
|
H, Baumann
|
|
B, Bolz
|
|
S, Artemyev
|
|
N, Kohl
|
|
S, Heckenlively
|
|
J, Wissinger
|
|
B. A homologous genetic basis of the murine cpfl1 mutant and human achromatopsia linked to mutations in the PDE6C gene.
|
|
Proc Natl Acad Sci U S A.
|
|
2009;106:19581–6.
|
|
[<a href="/pmc/articles/PMC2780790/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2780790</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19887631" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19887631</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.chiang.2017.400">Chiang
|
|
WC, Chan
|
|
P, Wissinger
|
|
B, Vincent
|
|
A, Skorczyk-Werner
|
|
A, Krawczyński
|
|
MR, Kaufman
|
|
RJ, Tsang
|
|
SH, Héon
|
|
E, Kohl
|
|
S, Lin
|
|
JH. Achromatopsia mutations target sequential steps of ATF6 activation.
|
|
Proc Natl Acad Sci U S A.
|
|
2017;114:400–5.
|
|
[<a href="/pmc/articles/PMC5240680/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5240680</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28028229" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28028229</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.faillace.2004.22643">Faillace
|
|
MP, Bernabeu
|
|
RO, Korenbrot
|
|
JI. Cellular processing of cone photoreceptor cyclic GMP-gated ion channels: a role for the S4 structural motif.
|
|
J Biol Chem.
|
|
2004;279:22643–53.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15024024" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15024024</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.genead.2011.7298">Genead
|
|
MA, Fishman
|
|
GA, Rha
|
|
J, Dubis
|
|
AM, Bonci
|
|
DM, Dubra
|
|
A, Stone
|
|
EM, Neitz
|
|
M, Carroll
|
|
J. Photoreceptor structure and function in patients with congenital achromatopsia.
|
|
Invest Ophthalmol Vis Sci.
|
|
2011;52:7298–308.
|
|
[<a href="/pmc/articles/PMC3183969/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3183969</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21778272" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21778272</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.gl_ckle.2014.99">Glöckle
|
|
N, Kohl
|
|
S, Mohr
|
|
J, Scheurenbrand
|
|
T, Sprecher
|
|
A, Weisschuh
|
|
N, Bernd
|
|
A, Rudolph
|
|
G, Schubach
|
|
M, Poloschek
|
|
C, Zrenner
|
|
E, Biskup
|
|
S, Berger
|
|
W, Wissinger
|
|
B, Neidhardt
|
|
J. Panel-based next generation sequencing as a reliable and efficient technique to detect mutations in unselected patients with retinal dystrophies.
|
|
Eur J Hum Genet.
|
|
2014;22:99–104.
|
|
[<a href="/pmc/articles/PMC3865404/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3865404</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23591405" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23591405</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.grau.2011.719">Grau
|
|
T, Artemyev
|
|
NO, Rosenberg
|
|
T, Dollfus
|
|
H, Haugen
|
|
OH, Cumhur Sener
|
|
E, Jurklies
|
|
B, Andreasson
|
|
S, Kernstock
|
|
C, Larsen
|
|
M, Zrenner
|
|
E, Wissinger
|
|
B, Kohl
|
|
S. Decreased catalytic activity and altered activation properties of PDE6C mutants associated with autosomal recessive achromatopsia.
|
|
Hum Mol Genet.
|
|
2011;20:719–30.
|
|
[<a href="/pmc/articles/PMC3269206/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3269206</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21127010" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21127010</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.greenberg.2014.437">Greenberg
|
|
JP, Sherman
|
|
J, Zweifel
|
|
SA, Chen
|
|
RW, Duncker
|
|
T, Kohl
|
|
S, Baumann
|
|
B, Wissinger
|
|
B, Yannuzzi
|
|
LA, Tsang
|
|
SH. Spectral-domain optical coherence tomography staging and autofluorescence imaging in achromatopsia.
|
|
JAMA Ophthalmol.
|
|
2014;132:437–45.
|
|
[<a href="/pmc/articles/PMC4423754/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4423754</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24504161" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24504161</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.holopigian.2004.275">Holopigian
|
|
K, Greenstein
|
|
VC, Seiple
|
|
W, Hood
|
|
DC, Carr
|
|
RE. Rod and cone photoreceptor function in patients with cone dystrophy.
|
|
Invest Ophthalmol Vis Sci.
|
|
2004;45:275–81.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/14691184" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14691184</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.huang.2013.e65546">Huang
|
|
L, Zhang
|
|
Q, Li
|
|
S, Guan
|
|
L, Xiao
|
|
X, Zhang
|
|
J, Jia
|
|
X, Sun
|
|
W, Zhu
|
|
Z, Gao
|
|
Y, Yin
|
|
Y, Wang
|
|
P, Guo
|
|
X, Wang
|
|
J, Zhang
|
|
Q.
|
|
Exome sequencing of 47 Chinese families with cone-rod dystrophy: mutations in 25 known causative genes.
|
|
PLoS One.
|
|
2013;8:e65546.
|
|
[<a href="/pmc/articles/PMC3679152/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3679152</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23776498" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23776498</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.johnson.2004.e20">Johnson
|
|
S, Michaelides
|
|
M, Aligianis
|
|
IA, Ainsworth
|
|
JR, Mollon
|
|
JD, Maher
|
|
ER, Moore
|
|
AT, Hunt
|
|
DM. Achromatopsia caused by novel mutations in both CNGA3 and CNGB3.
|
|
J Med Genet.
|
|
2004;41:e20.
|
|
[<a href="/pmc/articles/PMC1735666/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1735666</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/14757870" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14757870</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.khan.2007.3864">Khan
|
|
NW, Wissinger
|
|
B, Kohl
|
|
S, Sieving
|
|
PA. CNGB3 achromatopsia with progressive loss of residual cone function and impaired rod-mediated function.
|
|
Invest Ophthalmol Vis Sci.
|
|
2007;48:3864–71.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/17652762" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17652762</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.koeppen.2008.2391">Koeppen
|
|
K, Reuter
|
|
P, Kohl
|
|
S, Baumann
|
|
B, Ladewig
|
|
T, Wissinger
|
|
B. Functional analysis of human CNGA3 mutations associated with colour blindness suggests impaired surface expression of channel mutants A3(R427C) and A3(R563C).
|
|
Eur J Neurosci.
|
|
2008;27:2391–401.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/18445228" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18445228</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.koeppen.2010.830">Koeppen
|
|
K, Reuter
|
|
P, Ladewig
|
|
T, Kohl
|
|
S, Baumann
|
|
B, Jacobson
|
|
SG, Plomp
|
|
AS, Hamel
|
|
CP, Janecke
|
|
AR, Wissinger
|
|
B. Dissecting the pathogenic mechanisms of mutations in the pore region of the human cone photoreceptor cyclic nucleotide-gated channel.
|
|
Hum Mutat.
|
|
2010;31:830–9.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/20506298" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20506298</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.kohl.2000.2107">Kohl
|
|
S, Baumann
|
|
B, Broghammer
|
|
M, Jägle
|
|
H, Sieving
|
|
P, Kellner
|
|
U, Spegal
|
|
R, Anastasi
|
|
M, Zrenner
|
|
E, Sharpe
|
|
LT, Wissinger
|
|
B. Mutations in the CNGB3 gene encoding the beta-subunit of the cone photoreceptor cGMP-gated channel are responsible for achromatopsia (ACHM3) linked to chromosome 8q21.
|
|
Hum Mol Genet.
|
|
2000;9:2107–16.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/10958649" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10958649</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.kohl.2002.422">Kohl
|
|
S, Baumann
|
|
B, Rosenberg
|
|
T, Kellner
|
|
U, Lorenz
|
|
B, Vadala
|
|
M, Jacobson
|
|
SG, Wissinger
|
|
B. Mutations in the cone photoreceptor G-protein alpha-subunit gene GNAT2 in patients with achromatopsia.
|
|
Am J Hum Genet.
|
|
2002;71:422–5.
|
|
[<a href="/pmc/articles/PMC379175/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC379175</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/12077706" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12077706</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.kohl.2012.527">Kohl
|
|
S, Coppieters
|
|
F, Meire
|
|
F, Schaich
|
|
S, Roosing
|
|
S, Brennenstuhl
|
|
C, Bolz
|
|
S, van Genderen
|
|
MM, Riemslag
|
|
FCC, Lukowski
|
|
R, den Hollander
|
|
AI, Cremers
|
|
FPM, De Baere
|
|
E, Hoyng
|
|
CB, Wissinger
|
|
B, et al.
|
|
A nonsense mutation in PDE6H causes autosomal-recessive incomplete achromatopsia.
|
|
Am J Hum Genet.
|
|
2012;91:527–32.
|
|
[<a href="/pmc/articles/PMC3511981/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3511981</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22901948" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22901948</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.kohl.1998.257">Kohl
|
|
S, Marx
|
|
T, Giddings
|
|
I, Jägle
|
|
H, Jacobson
|
|
SG, Apfelstedt-Sylla
|
|
E, Zrenner
|
|
E, Sharpe
|
|
LT, Wissinger
|
|
B. Total colourblindness is caused by mutations in the gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated cation channel.
|
|
Nat Genet.
|
|
1998;19:257–9.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/9662398" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9662398</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.kohl.2005.302">Kohl
|
|
S, Varsanyi
|
|
B, Antunes
|
|
GA, Baumann
|
|
B, Hoyng
|
|
CB, Jägle
|
|
H, Rosenberg
|
|
T, Kellner
|
|
U, Lorenz
|
|
B, Salati
|
|
R, Jurklies
|
|
B, Farkas
|
|
A, Andreasson
|
|
S, Weleber
|
|
RG, Jacobson
|
|
SG, Rudolph
|
|
G, Castellan
|
|
C, Dollfus
|
|
H, Legius
|
|
E, Anastasi
|
|
M, Bitoun
|
|
P, Lev
|
|
D, Sieving
|
|
PA, Munier
|
|
FL, Zrenner
|
|
E, Sharpe
|
|
LT, Cremers
|
|
FP, Wissinger
|
|
B. CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia.
|
|
Eur J Hum Genet.
|
|
2005;13:302–8.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15657609" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15657609</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.kohl.2015.757">Kohl
|
|
S, Zobor
|
|
D, Chiang
|
|
WC, Weisschuh
|
|
N, Staller
|
|
J, Menendez
|
|
IG, Chang
|
|
S, Beck
|
|
SC, Garrido
|
|
MG, Sothilingam
|
|
V, Seeliger
|
|
MW, Stanzial
|
|
F, Benedicenti
|
|
F, Inzana
|
|
F, Héon
|
|
E, Vincent
|
|
A, Beis
|
|
J, Strom
|
|
TM, Rudolph
|
|
G, Roosing
|
|
S, Hollander
|
|
AI, Cremers
|
|
FP, Lopez
|
|
I, Ren
|
|
H, Moore
|
|
AT, Webster
|
|
AR, Michaelides
|
|
M, Koenekoop
|
|
RK, Zrenner
|
|
E, Kaufman
|
|
RJ, Tsang
|
|
SH, Wissinger
|
|
B, Lin
|
|
JH. Mutations in the unfolded protein response regulator ATF6 cause the cone dysfunction disorder achromatopsia.
|
|
Nat Genet.
|
|
2015;47:757–65.
|
|
[<a href="/pmc/articles/PMC4610820/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4610820</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26029869" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26029869</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.kom_romy.2010.2581">Komáromy
|
|
AM, Alexander
|
|
JJ, Rowlan
|
|
JS, Garcia
|
|
MM, Chiodo
|
|
VA, Kaya
|
|
A, Tanaka
|
|
JC, Acland
|
|
GM, Hauswirth
|
|
WW, Aguirre
|
|
GD. Gene therapy rescues cone function in congenital achromatopsia.
|
|
Hum Mol Genet.
|
|
2010;19:2581–93.
|
|
[<a href="/pmc/articles/PMC2883338/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2883338</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20378608" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20378608</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.lamb.2006.5137">Lamb
|
|
TD, Pugh
|
|
EN
|
|
Jr. Phototransduction, dark adaptation, and rhodopsin regeneration the proctor lecture.
|
|
Invest Ophthalmol Vis Sci.
|
|
2006;47:5137–52.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/17122096" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17122096</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.langlo.2016.3984">Langlo
|
|
CS, Patterson
|
|
EJ, Higgins
|
|
BP, Summerfelt
|
|
P, Razeen
|
|
MM, Erker
|
|
LR, Parker
|
|
M, Collison
|
|
FT, Fishman
|
|
GA, Kay
|
|
CN, Zhang
|
|
J, Weleber
|
|
RG, Yang
|
|
P, Wilson
|
|
DJ, Pennesi
|
|
ME, Lam
|
|
BL, Chiang
|
|
J, Chulay
|
|
JD, Dubra
|
|
A, Hauswirth
|
|
WW, Carroll
|
|
J., ACHM-001 Study Group. Residual foveal cone structure in CNGB3-associated achromatopsia.
|
|
Invest Ophthalmol Vis Sci.
|
|
2016;57:3984–95.
|
|
[<a href="/pmc/articles/PMC4978151/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4978151</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27479814" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27479814</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.lee.2015.2145">Lee
|
|
H, Purohit
|
|
R, Sheth
|
|
V, McLean
|
|
RJ, Kohl
|
|
S, Leroy
|
|
BP, Sundaram
|
|
V, Michaelides
|
|
M, Proudlock
|
|
FA, Gottlob
|
|
I. Retinal development in infants and young children with achromatopsia.
|
|
Ophthalmology.
|
|
2015;122:2145–7.
|
|
[<a href="/pmc/articles/PMC4582068/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4582068</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25972256" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25972256</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.liang.2015.571">Liang
|
|
X, Dong
|
|
F, Li
|
|
H, Li
|
|
H, Yang
|
|
L, Sui
|
|
R.
|
|
Novel CNGA3 mutations in Chinese patients with achromatopsia.
|
|
Br J Ophthalmol.
|
|
2015;99:571–6.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/25637600" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25637600</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.liu.2005.c187">Liu
|
|
C, Varnum
|
|
MD. Functional consequences of progressive cone dystrophy-associated mutations in the human cone photoreceptor cyclic nucleotide-gated channel CNGA3 subunit.
|
|
Am J Physiol Cell Physiol.
|
|
2005;289:C187–98.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15743887" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15743887</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.mayer.2017.1579">Mayer
|
|
AK, Van Cauwenbergh
|
|
C, Rother
|
|
C, Baumann
|
|
B, Reuter
|
|
P, De Baere
|
|
E, Wissinger
|
|
B, Kohl
|
|
S., ACHM Study Group. CNGB3 mutation spectrum including copy number variations in 552 achromatopsia patients.
|
|
Hum Mutat.
|
|
2017;38:1579–91.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/28795510" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28795510</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.michaelides.2004.1975">Michaelides
|
|
M, Aligianis
|
|
IA, Ainsworth
|
|
JR, Good
|
|
P, Mollon
|
|
JD, Maher
|
|
ER, Moore
|
|
AT, Hunt
|
|
DM. Progressive cone dystrophy associated with mutation in CNGB3.
|
|
Invest Ophthalmol Vis Sci.
|
|
2004;45:1975–82.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15161866" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15161866</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.michaelides.2003.1317">Michaelides
|
|
M, Aligianis
|
|
IA, Holder
|
|
GE, Simunovic
|
|
M, Mollon
|
|
JD, Maher
|
|
ER, Hunt
|
|
DM, Moore
|
|
AT. Cone dystrophy phenotype associated with a frameshift mutation (M280fsX291) in the alpha-subunit of cone specific transducin (GNAT2).
|
|
Br J Ophthalmol.
|
|
2003;87:1317–20.
|
|
[<a href="/pmc/articles/PMC1771876/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1771876</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/14609822" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14609822</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.michalakis.2005.1516">Michalakis
|
|
S, Geiger
|
|
H, Haverkamp
|
|
S, Hofmann
|
|
F, Gerstner
|
|
A, Biel
|
|
M. Impaired opsin targeting and cone photoreceptor migration in the retina of mice lacking the cyclic nucleotide-gated channel CNGA3.
|
|
Invest Ophthalmol Vis Sci.
|
|
2005;46:1516–24.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15790924" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15790924</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.michalakis.2012.183">Michalakis
|
|
S, Mühlfriedel
|
|
R, Tanimoto
|
|
N, Krishnamoorthy
|
|
V, Koch
|
|
S, Fischer
|
|
MD, Becirovic
|
|
E, Bai
|
|
L, Huber
|
|
G, Beck
|
|
SC, Fahl
|
|
E, Büning
|
|
H, Schmidt
|
|
J, Zong
|
|
X, Gollisch
|
|
T, Biel
|
|
M, Seeliger
|
|
MW. Gene therapy restores missing cone-mediated vision in the CNGA3-/- mouse model of achromatopsia.
|
|
Adv Exp Med Biol.
|
|
2012;723:183–9.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/22183332" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22183332</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.nasser.2018.e445">Nasser
|
|
F, Weisschuh
|
|
N, Maffei
|
|
P, Milan
|
|
G, Heller
|
|
C, Zrenner
|
|
E, Kohl
|
|
S, Kuehlewein
|
|
L. Ophthalmic features of cone-rod dystrophy caused by pathogenic variants in the ALMS1 gene.
|
|
Acta Ophthalmol.
|
|
2018;96:e445–54.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/29193673" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29193673</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.nishiguchi.2005.248">Nishiguchi
|
|
KM, Sandberg
|
|
MA, Gorji
|
|
N, Berson
|
|
EL, Dryja
|
|
TP. Cone cGMP-gated channel mutations and clinical findings in patients with achromatopsia, macular degeneration, and other hereditary cone diseases.
|
|
Hum Mutat.
|
|
2005;25:248–58.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15712225" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15712225</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.okada.2004.2324">Okada
|
|
A, Ueyama
|
|
H, Toyoda
|
|
F, Oda
|
|
S, Ding
|
|
WG, Tanabe
|
|
S, Yamade
|
|
S, Matsuura
|
|
H, Ohkubo
|
|
I, Kani
|
|
K. Functional role of hCngb3 in regulation of human cone cng channel: effect of rod monochromacy-associated mutations in hCNGB3 on channel function.
|
|
Invest Ophthalmol Vis Sci.
|
|
2004;45:2324–32.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15223812" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15223812</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.ouechtati.2011.22">Ouechtati
|
|
F, Merdassi
|
|
A, Bouyacoub
|
|
Y, Largueche
|
|
L, Derouiche
|
|
K, Ouragini
|
|
H, Nouira
|
|
S, Tiab
|
|
L, Baklouti
|
|
K, Rebai
|
|
A, Schorderet
|
|
DF, Munier
|
|
FL, Zografos
|
|
L, Abdelhak
|
|
S, El Matri
|
|
L. Clinical and genetic investigation of a large Tunisian family with complete achromatopsia: identification of a new nonsense mutation in GNAT2 gene.
|
|
J Hum Genet.
|
|
2011;56:22–8.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/21107338" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21107338</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.patel.2005.2282">Patel
|
|
KA, Bartoli
|
|
KM, Fandino
|
|
RA, Ngatchou
|
|
AN, Woch
|
|
G, Carey
|
|
J, Tanaka
|
|
JC. Transmembrane S1 mutations in CNGA3 from achromatopsia 2 patients cause loss of function and impaired cellular trafficking of the cone CNG channel.
|
|
Invest Ophthalmol Vis Sci.
|
|
2005;46:2282–90.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15980212" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15980212</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.pedurupillay.2016.e41">Pedurupillay
|
|
CR, Landsend
|
|
EC, Vigeland
|
|
MD, Ansar
|
|
M, Frengen
|
|
E, Misceo
|
|
D, Strømme
|
|
P. Segregation of incomplete achromatopsia and alopecia due to PDE6H and LPAR6 variants in a consanguineous family from Pakistan.
|
|
Genes (Basel). 2016;7:E41. pii.
|
|
[<a href="/pmc/articles/PMC4999829/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4999829</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27472364" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27472364</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.peng.2003.34533">Peng
|
|
C, Rich
|
|
ED, Varnum
|
|
MD. Achromatopsia-associated mutation in the human cone photoreceptor cyclic nucleotide-gated channel CNGB3 subunit alters the ligand sensitivity and pore properties of heteromeric channels.
|
|
J Biol Chem.
|
|
2003;278:34533–40.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/12815043" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12815043</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.pi_a.2004.265">Piña
|
|
AL, Baumert
|
|
U, Loyer
|
|
M, Koenekoop
|
|
RK. A three base pair deletion encoding the amino acid (lysine-270) in the alpha-cone transducin gene.
|
|
Mol Vis.
|
|
2004;10:265–71.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15094710" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15094710</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.piriev.1995.429">Piriev
|
|
NI, Viczian
|
|
AS, Ye
|
|
J, Kerner
|
|
B, Korenberg
|
|
JR, Farber
|
|
DB. Gene structure and amino acid sequence of the human cone photoreceptor cGMP-phosphodiesterase alpha' subunit (PDEA2) and its chromosomal localization to 10q24.
|
|
Genomics.
|
|
1995;28:429–35.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/7490077" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7490077</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.reicher.2010.101">Reicher
|
|
S, Seroussi
|
|
E, Gootwine
|
|
E.
|
|
A mutation in gene CNGA3 is associated with day blindness in sheep.
|
|
Genomics.
|
|
2010;95:101–4.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/19874885" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19874885</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.reuter.2008.1228">Reuter
|
|
P, Koeppen
|
|
K, Ladewig
|
|
T, Kohl
|
|
S, Baumann
|
|
B, Wissinger
|
|
B., Achromatopsia Clinical Study Group. Mutations in CNGA3 impair trafficking or function of cone cyclic nucleotide-gated channels, resulting in achromatopsia.
|
|
Hum Mutat.
|
|
2008;29:1228–36.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/18521937" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18521937</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.richards.2015.405">Richards
|
|
S, Aziz
|
|
N, Bale
|
|
S, Bick
|
|
D, Das
|
|
S, Gastier-Foster
|
|
J, Grody
|
|
WW, Hegde
|
|
M, Lyon
|
|
E, Spector
|
|
E, Voelkerding
|
|
K, Rehm
|
|
HL, et al.
|
|
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
|
|
Genet Med.
|
|
2015;17:405–24.
|
|
[<a href="/pmc/articles/PMC4544753/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4544753</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25741868" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25741868</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.rojas.2002.638">Rojas
|
|
CV, Maria
|
|
LS, Santos
|
|
JL, Cortes
|
|
F, Alliende
|
|
MA. A frameshift insertion in the cone cyclic nucleotide gated cation channel causes complete achromatopsia in a consanguineous family from a rural isolate.
|
|
Eur J Hum Genet.
|
|
2002;10:638–42.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/12357335" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12357335</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.rosenberg.2004.4256">Rosenberg
|
|
T, Baumann
|
|
B, Kohl
|
|
S, Zrenner
|
|
E, Jorgensen
|
|
AL, Wissinger
|
|
B. Variant phenotypes of incomplete achromatopsia in two cousins with GNAT2 gene mutations.
|
|
Invest Ophthalmol Vis Sci.
|
|
2004;45:4256–62.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15557429" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15557429</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.sharpe.1999">Sharpe LT, Stockman A, Jagle H, Nathans J. Opsin genes, cone photopigments, color vision, and color blindness. In: Gegenfurtner K, Sharpe LT, eds. Color Vision: from Genes to Perception. Cambridge, UK: Cambridge University Press; 1999:3-52.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.shimizumatsumoto.1996.121">Shimizu-Matsumoto
|
|
A, Itoh
|
|
K, Inazawa
|
|
J, Nishida
|
|
K, Matsumoto
|
|
Y, Kinoshita
|
|
S, Matsubara
|
|
K, Okubo
|
|
K. Isolation and chromosomal localization of the human cone cGMP phosphodiesterase gamma cDNA (PDE6H).
|
|
Genomics.
|
|
1996;32:121–4.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/8786098" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8786098</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.sidjanin.2002.1823">Sidjanin
|
|
DJ, Lowe
|
|
JK, McElwee
|
|
JL, Milne
|
|
BS, Phippen
|
|
TM, Sargan
|
|
DR, Aguirre
|
|
GD, Acland
|
|
GM, Ostrander
|
|
EA. Canine CNGB3 mutations establish cone degeneration as orthologous to the human achromatopsia locus ACHM3.
|
|
Hum Mol Genet.
|
|
2002;11:1823–33.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/12140185" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12140185</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.skorczykwerner.2017.1210">Skorczyk-Werner
|
|
A, Chiang
|
|
WC, Wawrocka
|
|
A, Wicher
|
|
K, Jarmuż-Szymczak
|
|
M, Kostrzewska-Poczekaj
|
|
M, Jamsheer
|
|
A, Płoski
|
|
R, Rydzanicz
|
|
M, Pojda-Wilczek
|
|
D, Weisschuh
|
|
N, Wissinger
|
|
B, Kohl
|
|
S, Lin
|
|
JH, Krawczyński
|
|
MR. Autosomal recessive cone-rod dystrophy can be caused by mutations in the ATF6 gene.
|
|
Eur J Hum Genet.
|
|
2017;25:1210–6.
|
|
[<a href="/pmc/articles/PMC5643965/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5643965</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28812650" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28812650</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.sundaram.2014.234">Sundaram
|
|
V, Wilde
|
|
C, Aboshiha
|
|
J, Cowing
|
|
J, Han
|
|
C, Langlo
|
|
CS, Chana
|
|
R, Davidson
|
|
AE, Sergouniotis
|
|
PI, Bainbridge
|
|
JW, Ali
|
|
RR, Dubra
|
|
A, Rubin
|
|
G, Webster
|
|
AR, Moore
|
|
AT, Nardini
|
|
M, Carroll
|
|
J, Michaelides
|
|
M. Retinal structure and function in achromatopsia: implications for gene therapy.
|
|
Ophthalmology.
|
|
2014;121:234–45.
|
|
[<a href="/pmc/articles/PMC3895408/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3895408</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24148654" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24148654</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.sundin.2000.289">Sundin
|
|
OH, Yang
|
|
JM, Li
|
|
Y, Zhu
|
|
D, Hurd
|
|
JN, Mitchell
|
|
TN, Silva
|
|
ED, Maumenee
|
|
IH. Genetic basis of total colourblindness among the Pingelapese islanders.
|
|
Nat Genet.
|
|
2000;25:289–93.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/10888875" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10888875</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.taylor.2017.985">Taylor
|
|
RL, Parry
|
|
NRA, Barton
|
|
SJ, Campbell
|
|
C, Delaney
|
|
CM, Ellingford
|
|
JM, Hall
|
|
G, Hardcastle
|
|
C, Morarji
|
|
J, Nichol
|
|
EJ, Williams
|
|
LC, Douzgou
|
|
S, Clayton-Smith
|
|
J, Ramsden
|
|
SC, Sharma
|
|
V, Biswas
|
|
S, Lloyd
|
|
IC, Ashworth
|
|
JL, Black
|
|
GC, Sergouniotis
|
|
PI. Panel-based clinical genetic testing in 85 children with inherited retinal disease.
|
|
Ophthalmology.
|
|
2017;124:985–91.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/28341476" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28341476</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.thiadens.2009a.240">Thiadens
|
|
AA, den Hollander
|
|
AI, Roosing
|
|
S, Nabuurs
|
|
SB, Zekveld-Vroon
|
|
RC, Collin
|
|
RW, De Baere
|
|
E, Koenekoop
|
|
RK, van Schooneveld
|
|
MJ, Strom
|
|
TM, van Lith-Verhoeven
|
|
JJ, Lotery
|
|
AJ, van Moll-Ramirez
|
|
N, Leroy
|
|
BP, van den Born
|
|
LI, Hoyng
|
|
CB, Cremers
|
|
FP, Klaver
|
|
CC. Homozygosity mapping reveals PDE6C mutations in patients with early-onset cone photoreceptor disorders.
|
|
Am J Hum Genet.
|
|
2009a;85:240–7.
|
|
[<a href="/pmc/articles/PMC2725240/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2725240</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19615668" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19615668</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.thiadens.2010.825">Thiadens
|
|
AA, Roosing
|
|
S, Collin
|
|
RW, van Moll-Ramirez
|
|
N, van Lith-Verhoeven
|
|
JJ, van Schooneveld
|
|
MJ, den Hollander
|
|
AI, van den Born
|
|
LI, Hoyng
|
|
CB, Cremers
|
|
FP, Klaver
|
|
CC. Comprehensive analysis of the achromatopsia genes CNGA3 and CNGB3 in progressive cone dystrophy.
|
|
Ophthalmology.
|
|
2010;117:825–30.e1.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/20079539" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20079539</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.thiadens.2009b.1984">Thiadens
|
|
AA, Slingerland
|
|
NW, Roosing
|
|
S, van Schooneveld
|
|
MJ, van Lith-Verhoeven
|
|
JJ, van Moll-Ramirez
|
|
N, van den Born
|
|
LI, Hoyng
|
|
CB, Cremers
|
|
FP, Klaver
|
|
CC. Genetic etiology and clinical consequences of complete and incomplete achromatopsia.
|
|
Ophthalmology.
|
|
2009b;116:1984–9.e1.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/19592100" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19592100</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.thomas.2011.882">Thomas
|
|
MG, Kumar
|
|
A, Kohl
|
|
S, Proudlock
|
|
FA, Gottlob
|
|
I. High-resolution in vivo imaging in achromatopsia.
|
|
Ophthalmology.
|
|
2011;118:882–7.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/21211844" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21211844</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.thomas.2012.1232">Thomas
|
|
MG, McLean
|
|
RJ, Kohl
|
|
S, Sheth
|
|
V, Gottlob
|
|
I. Early signs of longitudinal progressive cone photoreceptor degeneration in achromatopsia.
|
|
Br J Ophthalmol.
|
|
2012;96:1232–6.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/22790432" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22790432</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.tr_nkner.2004.138">Tränkner
|
|
D, Jägle
|
|
H, Kohl
|
|
S, Apfelstedt-Sylla
|
|
E, Sharpe
|
|
LT, Kaupp
|
|
UB, Zrenner
|
|
E, Seifert
|
|
R, Wissinger
|
|
B. Molecular basis of an inherited form of incomplete achromatopsia.
|
|
J Neurosci.
|
|
2004;24:138–47.
|
|
[<a href="/pmc/articles/PMC6729583/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6729583</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/14715947" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14715947</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.ueno.2017.92">Ueno
|
|
S, Nakanishi
|
|
A, Kominami
|
|
T, Ito
|
|
Y, Hayashi
|
|
T, Yoshitake
|
|
K, Kawamura
|
|
Y, Tsunoda
|
|
K, Iwata
|
|
T, Terasaki
|
|
H. In vivo imaging of a cone mosaic in a patient with achromatopsia associated with a GNAT2 variant.
|
|
Jpn J Ophthalmol.
|
|
2017;61:92–8.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/27718025" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27718025</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.vars_nyi.2005.996">Varsányi
|
|
B, Wissinger
|
|
B, Kohl
|
|
S, Koeppen
|
|
K, Farkas
|
|
A. Clinical and genetic features of Hungarian achromatopsia patients.
|
|
Mol Vis.
|
|
2005;11:996–1001.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/16319819" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16319819</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.vincent.2011.107">Vincent
|
|
A, Wright
|
|
T, Billingsley
|
|
G, Westall
|
|
C, Héon
|
|
E. Oligocone trichromacy is part of the spectrum of CNGA3-related cone system disorders.
|
|
Ophthalmic Genet.
|
|
2011;32:107–13.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/21268679" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21268679</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.walter.2011.1081">Walter
|
|
P, Ron
|
|
D. The unfolded protein response: from stress pathway to homeostatic regulation.
|
|
Science.
|
|
2011;334:1081–6.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/22116877" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22116877</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.wang.2012.857">Wang
|
|
S, Kaufman
|
|
RJ. The impact of the unfolded protein response on human disease.
|
|
J Cell Biol.
|
|
2012;197:857–67.
|
|
[<a href="/pmc/articles/PMC3384412/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3384412</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22733998" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22733998</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.weisschuh.2016.e0145951">Weisschuh
|
|
N, Mayer
|
|
AK, Strom
|
|
TM, Kohl
|
|
S, Glöckle
|
|
N, Schubach
|
|
M, Andreasson
|
|
S, Bernd
|
|
A, Birch
|
|
DG, Hamel
|
|
CP, Heckenlively
|
|
JR, Jacobson
|
|
SG, Kamme
|
|
C, Kellner
|
|
U, Kunstmann
|
|
E, Maffei
|
|
P, Reiff
|
|
CM, Rohrschneider
|
|
K, Rosenberg
|
|
T, Rudolph
|
|
G, Vámos
|
|
R, Varsányi
|
|
B, Weleber
|
|
RG, Wissinger
|
|
B. Mutation detection in patients with retinal dystrophies using targeted next generation sequencing.
|
|
PLoS One.
|
|
2016;11:e0145951.
|
|
[<a href="/pmc/articles/PMC4713063/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4713063</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26766544" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26766544</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.weisschuh.2018.1366">Weisschuh
|
|
N, Stingl
|
|
K, Audo
|
|
I, Biskup
|
|
S, Bocquet
|
|
B, Branham
|
|
K, Burstedt
|
|
MS, De Baere
|
|
E, De Vries
|
|
MJ, Golovleva
|
|
I, Green
|
|
A, Heckenlively
|
|
J, Leroy
|
|
BP, Meunier
|
|
I, Traboulsi
|
|
E, Wissinger
|
|
B, Kohl
|
|
S. Mutations in the gene PDE6C encoding the catalytic subunit of the cone photoreceptor phosphodiesterase in patients with achromatopsia.
|
|
Hum Mutat.
|
|
2018;39:1366–71.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/30080950" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30080950</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.wissinger.2001.722">Wissinger
|
|
B, Gamer
|
|
D, Jagle
|
|
H, Giorda
|
|
R, Marx
|
|
T, Mayer
|
|
S, Tippmann
|
|
S, Broghammer
|
|
M, Jurklies
|
|
B, Rosenberg
|
|
T, Jacobson
|
|
SG, Sener
|
|
EC, Tatlipinar
|
|
S, Hoyng
|
|
CB, Castellan
|
|
C, Bitoun
|
|
P, Andreasson
|
|
S, Rudolph
|
|
G, Kellner
|
|
U, Lorenz
|
|
B, Wolff
|
|
G, Verellen-Dumoulin
|
|
C, Schwartz
|
|
M, Cremers
|
|
FP, Apfelstedt-Sylla
|
|
E, Zrenner
|
|
E, Salati
|
|
R, Sharpe
|
|
LT, Kohl
|
|
S. CNGA3 mutations in hereditary cone photoreceptor disorders.
|
|
Am J Hum Genet.
|
|
2001;69:722–37.
|
|
[<a href="/pmc/articles/PMC1226059/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1226059</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/11536077" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11536077</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.wiszniewski.2007.433">Wiszniewski
|
|
W, Lewis
|
|
RA, Lupski
|
|
JR. Achromatopsia: the CNGB3 p.T383fsX mutation results from a founder effect and is responsible for the visual phenotype in the original report of uniparental disomy 14.
|
|
Hum Genet.
|
|
2007;121:433–9.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/17265047" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17265047</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.xu.2015.3889">Xu
|
|
M, Gelowani
|
|
V, Eblimit
|
|
A, Wang
|
|
F, Young
|
|
MP, Sawyer
|
|
BL, Zhao
|
|
L, Jenkins
|
|
G, Creel
|
|
DJ, Wang
|
|
K, Ge
|
|
Z, Wang
|
|
H, Li
|
|
Y, Hartnett
|
|
ME, Chen
|
|
R. ATF6 Is Mutated in Early Onset Photoreceptor Degeneration With Macular Involvement.
|
|
Invest Ophthalmol Vis Sci.
|
|
2015;56:3889–95.
|
|
[<a href="/pmc/articles/PMC4468593/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4468593</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26070061" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26070061</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.zein.2014.6301">Zein
|
|
WM, Jeffrey
|
|
BG, Wiley
|
|
HE, Turriff
|
|
AE, Tumminia
|
|
SJ, Tao
|
|
W, Bush
|
|
RA, Marangoni
|
|
D, Wen
|
|
R, Wei
|
|
LL, Sieving
|
|
PA. CNGB3-achromatopsia clinical trial with CNTF: diminished rod pathway responses with no evidence of improvement in cone function.
|
|
Invest Ophthalmol Vis Sci.
|
|
2014;55:6301–8.
|
|
[<a href="/pmc/articles/PMC4191169/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4191169</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25205868" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25205868</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.zelinger.2015.997">Zelinger
|
|
L, Cideciyan
|
|
AV, Kohl
|
|
S, Schwartz
|
|
SB, Rosenmann
|
|
A, Eli
|
|
D, Sumaroka
|
|
A, Roman
|
|
AJ, Luo
|
|
X, Brown
|
|
C, Rosin
|
|
B, Blumenfeld
|
|
A, Wissinger
|
|
B, Jacobson
|
|
SG, Banin
|
|
E, Sharon
|
|
D. Genetics and disease expression in the CNGA3 form of achromatopsia: steps on the path to gene therapy.
|
|
Ophthalmology.
|
|
2015;122:997–1007.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/25616768" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25616768</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="achm.REF.zobor.2017.821">Zobor
|
|
D, Werner
|
|
A, Stanzial
|
|
F, Benedicenti
|
|
F, Rudolph
|
|
G, Kellner
|
|
U, Hamel
|
|
C, Andréasson
|
|
S, Zobor
|
|
G, Strasser
|
|
T, Wissinger
|
|
B, Kohl
|
|
S, Zrenner
|
|
E.
|
|
RD-CURE Consortium (2017) The clinical phenotype of CNGA3-related achromatopsia: pretreatment characterization in preparation of a gene replacement therapy trial.
|
|
Invest Ophthalmol Vis Sci.
|
|
2017;58:821–32.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/28159970" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28159970</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK1418_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Susanne Kohl</span>, MSc, PhD<div class="affiliation small">Molecular Genetics Laboratory<br />Institute for Ophthalmic Research<br />University of Tübingen<br />Tübingen, Germany<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ed.negnibeut-inu@lhok.ennasus" class="oemail">ed.negnibeut-inu@lhok.ennasus</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Herbert Jägle</span>, MD, Dhabil, FEBO<div class="affiliation small">Department of Ophthalmology<br />University of Regensburg<br />Regensburg, Germany<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ed.rku@elgeaj.trebreh" class="oemail">ed.rku@elgeaj.trebreh</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Bernd Wissinger</span>, MSc, PhD<div class="affiliation small">Molecular Genetics Laboratory<br />Institute for Ophthalmic Research<br />University of Tübingen<br />Tübingen, Germany<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ed.negnibeut-inu@regnissiw" class="oemail">ed.negnibeut-inu@regnissiw</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Ditta Zobor</span>, MD, PhD, Dhabil, FEBO<div class="affiliation small">Institute for Ophthalmic Research<br />University of Tübingen<br />Tübingen, Germany<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ed.negnibeut-inu@roboz.attid" class="oemail">ed.negnibeut-inu@roboz.attid</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">June 24, 2004</span>; Last Update: <span itemprop="dateModified">September 20, 2018</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 1993-2025, University of Washington, Seattle. GeneReviews is
|
|
a registered trademark of the University of Washington, Seattle. All rights
|
|
reserved.<p class="small">GeneReviews® chapters are owned by the University of Washington. Permission is
|
|
hereby granted to reproduce, distribute, and translate copies of content materials for
|
|
noncommercial research purposes only, provided that (i) credit for source (<a href="http://www.genereviews.org/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">http://www.genereviews.org/</a>) and copyright (© 1993-2025 University of
|
|
Washington) are included with each copy; (ii) a link to the original material is provided
|
|
whenever the material is published elsewhere on the Web; and (iii) reproducers,
|
|
distributors, and/or translators comply with the <a href="https://www.ncbi.nlm.nih.gov/books/n/gene/GRcopyright_permiss/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">GeneReviews® Copyright Notice and Usage
|
|
Disclaimer</a>. No further modifications are allowed. For clarity, excerpts
|
|
of GeneReviews chapters for use in lab reports and clinic notes are a permitted
|
|
use.</p><p class="small">For more information, see the <a href="https://www.ncbi.nlm.nih.gov/books/n/gene/GRcopyright_permiss/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">GeneReviews® Copyright Notice and Usage
|
|
Disclaimer</a>.</p><p class="small">For questions regarding permissions or whether a specified use is allowed,
|
|
contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div></div><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>Kohl S, Jägle H, Wissinger B, et al. Achromatopsia. 2004 Jun 24 [Updated 2018 Sep 20]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/gene/achondroplasia/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gene/npab/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobachmTd"><div id="achm.Td" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1418/table/achm.Td/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__achm.Td_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_achm.Td_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Achromatopsia: Included Phenotypes <sup>1</sup></th></tr></thead><tbody><tr><td headers="hd_h_achm.Td_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><ul><li class="half_rhythm"><div>Complete achromatopsia (rod monochromatism, total color blindness)</div></li><li class="half_rhythm"><div>Incomplete achromatopsia</div></li></ul>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">For synonyms and outdated names see <a href="#achm.Nomenclature">Nomenclature</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="achm.TF.d.1"><p class="no_margin">For other genetic causes of these phenotypes see <a href="#achm.Differential_Diagnosis">Differential Diagnosis</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobachmTmoleculargenetictestingusedin"><div id="achm.T.molecular_genetic_testing_used_in" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Achromatopsia</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1418/table/achm.T.molecular_genetic_testing_used_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__achm.T.molecular_genetic_testing_used_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_2" style="text-align:left;vertical-align:middle;">Proportion of Achromatopsia Attributed to Pathogenic Variants in Gene <sup>2</sup> (Population)</th><th id="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>3</sup> Identified by Method</th></tr><tr><th headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_3" id="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>4</sup></th><th headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_3" id="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>5</sup></th></tr></thead><tbody><tr><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>ATF6</i>
|
|
</td><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1.5%</td><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_achm.T.molecular_genetic_testing_used_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">15/15 <sup>6</sup></td><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_achm.T.molecular_genetic_testing_used_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None reported <sup>7</sup></td></tr><tr><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>CNGA3</i>
|
|
</td><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5%-33% (European)<br />84% (Israeli & Palestinian) <sup>8</sup><br />80% (Chinese) <sup>9</sup></td><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_achm.T.molecular_genetic_testing_used_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~100% <sup>10</sup></td><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_achm.T.molecular_genetic_testing_used_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None reported <sup>7</sup></td></tr><tr><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>CNGB3</i>
|
|
</td><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">60% (European)<br />16% (Israeli & Palestinian) <sup>11</sup></td><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_achm.T.molecular_genetic_testing_used_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~95% <sup>12</sup></td><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_achm.T.molecular_genetic_testing_used_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">7 distinct deletions in 7 families; 3 duplications in 10 families <sup>13</sup></td></tr><tr><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>GNAT2</i>
|
|
</td><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1.8%</td><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_achm.T.molecular_genetic_testing_used_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~99%</td><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_achm.T.molecular_genetic_testing_used_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">3 families <sup>14</sup></td></tr><tr><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>PDE6C</i>
|
|
</td><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2.5% <sup>15</sup></td><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_achm.T.molecular_genetic_testing_used_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">All reported <sup>16</sup></td><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_achm.T.molecular_genetic_testing_used_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None reported <sup>7</sup></td></tr><tr><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>PDE6H</i>
|
|
</td><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">0.1%</td><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_achm.T.molecular_genetic_testing_used_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 17.</td><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_achm.T.molecular_genetic_testing_used_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None reported <sup>7</sup></td></tr><tr><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown</td><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10%-25% <sup>18</sup></td><td headers="hd_h_achm.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_achm.T.molecular_genetic_testing_used_in_1_1_2_1 hd_h_achm.T.molecular_genetic_testing_used_in_1_1_2_2" colspan="2" rowspan="1" style="text-align:left;vertical-align:middle;">NA</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="achm.TF.1.1"><p class="no_margin">See <a href="/books/NBK1418/?report=reader#achm.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="achm.TF.1.2"><p class="no_margin"><a class="bibr" href="#achm.REF.mayer.2017.1579" rid="achm.REF.mayer.2017.1579">Mayer et al [2017]</a> unless otherwise noted</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="achm.TF.1.3"><p class="no_margin">See <a href="#achm.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="achm.TF.1.4"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click <a href="/books/n/gene/app2/?report=reader">here</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="achm.TF.1.5"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="achm.TF.1.6"><p class="no_margin"><a class="bibr" href="#achm.REF.ansar.2015.941" rid="achm.REF.ansar.2015.941">Ansar et al [2015]</a>, <a class="bibr" href="#achm.REF.kohl.2015.757" rid="achm.REF.kohl.2015.757">Kohl et al [2015]</a>, <a class="bibr" href="#achm.REF.xu.2015.3889" rid="achm.REF.xu.2015.3889">Xu et al [2015]</a>, <a class="bibr" href="#achm.REF.carss.2017.75" rid="achm.REF.carss.2017.75">Carss et al [2017]</a>, <a class="bibr" href="#achm.REF.skorczykwerner.2017.1210" rid="achm.REF.skorczykwerner.2017.1210">Skorczyk-Werner et al [2017]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>7. </dt><dd><div id="achm.TF.1.7"><p class="no_margin">Larger deletions, insertions, or duplications have either not been reported or are confined to single reports or families [<a class="bibr" href="#achm.REF.rosenberg.2004.4256" rid="achm.REF.rosenberg.2004.4256">Rosenberg et al 2004</a>]. Consequently, the prevalence and detection rate for such pathogenic variants cannot be estimated.</p></div></dd></dl><dl class="bkr_refwrap"><dt>8. </dt><dd><div id="achm.TF.1.8"><p class="no_margin">
|
|
<a class="bibr" href="#achm.REF.zelinger.2015.997" rid="achm.REF.zelinger.2015.997">Zelinger et al [2015]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>9. </dt><dd><div id="achm.TF.1.9"><p class="no_margin"><a class="bibr" href="#achm.REF.kohl.1998.257" rid="achm.REF.kohl.1998.257">Kohl et al [1998]</a>, <a class="bibr" href="#achm.REF.wissinger.2001.722" rid="achm.REF.wissinger.2001.722">Wissinger et al [2001]</a>, <a class="bibr" href="#achm.REF.kohl.2005.302" rid="achm.REF.kohl.2005.302">Kohl et al [2005]</a>, <a class="bibr" href="#achm.REF.liang.2015.571" rid="achm.REF.liang.2015.571">Liang et al [2015]</a>, <a class="bibr" href="#achm.REF.zelinger.2015.997" rid="achm.REF.zelinger.2015.997">Zelinger et al [2015]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>10. </dt><dd><div id="achm.TF.1.10"><p class="no_margin"><a class="bibr" href="#achm.REF.kohl.1998.257" rid="achm.REF.kohl.1998.257">Kohl et al [1998]</a>, <a class="bibr" href="#achm.REF.wissinger.2001.722" rid="achm.REF.wissinger.2001.722">Wissinger et al [2001]</a>, <a class="bibr" href="#achm.REF.johnson.2004.e20" rid="achm.REF.johnson.2004.e20">Johnson et al [2004]</a>, <a class="bibr" href="#achm.REF.tr_nkner.2004.138" rid="achm.REF.tr_nkner.2004.138">Tränkner et al [2004]</a>, <a class="bibr" href="#achm.REF.nishiguchi.2005.248" rid="achm.REF.nishiguchi.2005.248">Nishiguchi et al [2005]</a>, <a class="bibr" href="#achm.REF.vars_nyi.2005.996" rid="achm.REF.vars_nyi.2005.996">Varsányi et al [2005]</a>, <a class="bibr" href="#achm.REF.ahuja.2008.1293" rid="achm.REF.ahuja.2008.1293">Ahuja et al [2008]</a>, <a class="bibr" href="#achm.REF.koeppen.2008.2391" rid="achm.REF.koeppen.2008.2391">Koeppen et al [2008]</a>, <a class="bibr" href="#achm.REF.reuter.2008.1228" rid="achm.REF.reuter.2008.1228">Reuter et al [2008]</a>, <a class="bibr" href="#achm.REF.koeppen.2010.830" rid="achm.REF.koeppen.2010.830">Koeppen et al [2010]</a>, <a class="bibr" href="#achm.REF.thiadens.2010.825" rid="achm.REF.thiadens.2010.825">Thiadens et al [2010]</a>, <a class="bibr" href="#achm.REF.genead.2011.7298" rid="achm.REF.genead.2011.7298">Genead et al [2011]</a>, <a class="bibr" href="#achm.REF.vincent.2011.107" rid="achm.REF.vincent.2011.107">Vincent et al [2011]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>11. </dt><dd><div id="achm.TF.1.11"><p class="no_margin"><a class="bibr" href="#achm.REF.kohl.2000.2107" rid="achm.REF.kohl.2000.2107">Kohl et al [2000]</a>, <a class="bibr" href="#achm.REF.kohl.2005.302" rid="achm.REF.kohl.2005.302">Kohl et al [2005]</a>, <a class="bibr" href="#achm.REF.thiadens.2009b.1984" rid="achm.REF.thiadens.2009b.1984">Thiadens et al [2009b]</a>, <a class="bibr" href="#achm.REF.zelinger.2015.997" rid="achm.REF.zelinger.2015.997">Zelinger et al [2015]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>12. </dt><dd><div id="achm.TF.1.12"><p class="no_margin">Of 163 individuals with pathogenic variants in <i>CNGB3</i>, 105 (64%) were homozygotes for <a href="/books/NBK1418/table/achm.T.cngb3_pathogenic_variants_discuss/?report=objectonly" target="object" rid-ob="figobachmTcngb3pathogenicvariantsdiscuss">c.1148delC</a>, 44 (27%) were compound heterozygotes, and in 14 (9%) only one pathogenic variant was identified [<a class="bibr" href="#achm.REF.mayer.2017.1579" rid="achm.REF.mayer.2017.1579">Mayer et al 2017</a>].</p></div></dd></dl><dl class="bkr_refwrap"><dt>13. </dt><dd><div id="achm.TF.1.13"><p class="no_margin"><a class="bibr" href="#achm.REF.kohl.2015.757" rid="achm.REF.kohl.2015.757">Kohl et al [2015]</a>, <a class="bibr" href="#achm.REF.mayer.2017.1579" rid="achm.REF.mayer.2017.1579">Mayer et al [2017]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>14. </dt><dd><div id="achm.TF.1.14"><p class="no_margin"><a class="bibr" href="#achm.REF.rosenberg.2004.4256" rid="achm.REF.rosenberg.2004.4256">Rosenberg et al [2004]</a>; S Kohl, unpublished data</p></div></dd></dl><dl class="bkr_refwrap"><dt>15. </dt><dd><div id="achm.TF.1.15"><p class="no_margin"><a class="bibr" href="#achm.REF.chang.2009.19581" rid="achm.REF.chang.2009.19581">Chang et al [2009]</a>, <a class="bibr" href="#achm.REF.thiadens.2009a.240" rid="achm.REF.thiadens.2009a.240">Thiadens et al [2009a]</a>, <a class="bibr" href="#achm.REF.grau.2011.719" rid="achm.REF.grau.2011.719">Grau et al [2011]</a>, <a class="bibr" href="#achm.REF.huang.2013.e65546" rid="achm.REF.huang.2013.e65546">Huang et al [2013]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>16. </dt><dd><div id="achm.TF.1.16"><p class="no_margin"><a class="bibr" href="#achm.REF.aligianis.2002.656" rid="achm.REF.aligianis.2002.656">Aligianis et al [2002]</a>, <a class="bibr" href="#achm.REF.kohl.2002.422" rid="achm.REF.kohl.2002.422">Kohl et al [2002]</a>, <a class="bibr" href="#achm.REF.michaelides.2003.1317" rid="achm.REF.michaelides.2003.1317">Michaelides et al [2003]</a>, <a class="bibr" href="#achm.REF.pi_a.2004.265" rid="achm.REF.pi_a.2004.265">Piña et al [2004]</a>, <a class="bibr" href="#achm.REF.rosenberg.2004.4256" rid="achm.REF.rosenberg.2004.4256">Rosenberg et al [2004]</a>, <a class="bibr" href="#achm.REF.ouechtati.2011.22" rid="achm.REF.ouechtati.2011.22">Ouechtati et al [2011]</a>, <a class="bibr" href="#achm.REF.langlo.2016.3984" rid="achm.REF.langlo.2016.3984">Langlo et al [2016]</a>, <a class="bibr" href="#achm.REF.bryant.2017.49" rid="achm.REF.bryant.2017.49">Bryant et al [2017]</a>, <a class="bibr" href="#achm.REF.carss.2017.75" rid="achm.REF.carss.2017.75">Carss et al [2017]</a>, <a class="bibr" href="#achm.REF.taylor.2017.985" rid="achm.REF.taylor.2017.985">Taylor et al [2017]</a>, <a class="bibr" href="#achm.REF.ueno.2017.92" rid="achm.REF.ueno.2017.92">Ueno et al [2017]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>17. </dt><dd><div id="achm.TF.1.17"><p class="no_margin">A single nonsense variant has been reported in three families [<a class="bibr" href="#achm.REF.kohl.2012.527" rid="achm.REF.kohl.2012.527">Kohl et al 2012</a>, <a class="bibr" href="#achm.REF.pedurupillay.2016.e41" rid="achm.REF.pedurupillay.2016.e41">Pedurupillay et al 2016</a>].</p></div></dd></dl><dl class="bkr_refwrap"><dt>18. </dt><dd><div id="achm.TF.1.18"><p class="no_margin"><a class="bibr" href="#achm.REF.kohl.2005.302" rid="achm.REF.kohl.2005.302">Kohl et al [2005]</a>, <a class="bibr" href="#achm.REF.thiadens.2009b.1984" rid="achm.REF.thiadens.2009b.1984">Thiadens et al [2009b]</a></p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobachmTallelicdisorderstoconsiderin"><div id="achm.T.allelic_disorders_to_consider_in" class="table"><h3><span class="label">Table 2a. </span></h3><div class="caption"><p>Allelic Disorders to Consider in the Differential Diagnosis of Achromatopsia</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1418/table/achm.T.allelic_disorders_to_consider_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__achm.T.allelic_disorders_to_consider_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_achm.T.allelic_disorders_to_consider_in_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_achm.T.allelic_disorders_to_consider_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder(s) <sup>1</sup></th><th id="hd_h_achm.T.allelic_disorders_to_consider_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_achm.T.allelic_disorders_to_consider_in_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">References</th></tr></thead><tbody><tr><td headers="hd_h_achm.T.allelic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>CNGA3</i>
|
|
</td><td headers="hd_h_achm.T.allelic_disorders_to_consider_in_1_1_1_2" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">Progressive cone dystrophy</td><td headers="hd_h_achm.T.allelic_disorders_to_consider_in_1_1_1_3" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_achm.T.allelic_disorders_to_consider_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#achm.REF.wissinger.2001.722" rid="achm.REF.wissinger.2001.722">Wissinger et al [2001]</a>, <a class="bibr" href="#achm.REF.nishiguchi.2005.248" rid="achm.REF.nishiguchi.2005.248">Nishiguchi et al [2005]</a></td></tr><tr><td headers="hd_h_achm.T.allelic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>CNGB3</i>
|
|
</td><td headers="hd_h_achm.T.allelic_disorders_to_consider_in_1_1_1_4" colspan="1" rowspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#achm.REF.michaelides.2004.1975" rid="achm.REF.michaelides.2004.1975">Michaelides et al [2004]</a>, <a class="bibr" href="#achm.REF.thiadens.2010.825" rid="achm.REF.thiadens.2010.825">Thiadens et al [2010]</a></td></tr><tr><td headers="hd_h_achm.T.allelic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>GNAT2</i>
|
|
</td><td headers="hd_h_achm.T.allelic_disorders_to_consider_in_1_1_1_4" colspan="1" rowspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a class="bibr" href="#achm.REF.pi_a.2004.265" rid="achm.REF.pi_a.2004.265">Piña et al [2004]</a>
|
|
</td></tr><tr><td headers="hd_h_achm.T.allelic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>PDE6C</i>
|
|
</td><td headers="hd_h_achm.T.allelic_disorders_to_consider_in_1_1_1_4" colspan="1" rowspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#achm.REF.thiadens.2009a.240" rid="achm.REF.thiadens.2009a.240">Thiadens et al [2009a]</a>, <a class="bibr" href="#achm.REF.huang.2013.e65546" rid="achm.REF.huang.2013.e65546">Huang et al [2013]</a></td></tr><tr><td headers="hd_h_achm.T.allelic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>ATF6</i>
|
|
</td><td headers="hd_h_achm.T.allelic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cone-rod dystrophy; macular dystrophy</td><td headers="hd_h_achm.T.allelic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_achm.T.allelic_disorders_to_consider_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#achm.REF.carss.2017.75" rid="achm.REF.carss.2017.75">Carss et al [2017]</a>, <a class="bibr" href="#achm.REF.skorczykwerner.2017.1210" rid="achm.REF.skorczykwerner.2017.1210">Skorczyk-Werner et al [2017]</a></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="achm.TF.2a.1"><p class="no_margin">Often only distinguishable from achromatopsia by evidence of disease progression over time</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AR = autosomal recessive ; MOI = mode of inheritance</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobachmTallelicdisordersnotinthediff"><div id="achm.T.allelic_disorders_not_in_the_diff" class="table"><h3><span class="label">Table 2b. </span></h3><div class="caption"><p>Allelic Disorders (Not in the Differential Diagnosis of Achromatopsia)</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1418/table/achm.T.allelic_disorders_not_in_the_diff/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__achm.T.allelic_disorders_not_in_the_diff_lrgtbl__"><table><thead><tr><th id="hd_h_achm.T.allelic_disorders_not_in_the_diff_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_achm.T.allelic_disorders_not_in_the_diff_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_achm.T.allelic_disorders_not_in_the_diff_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference</th></tr></thead><tbody><tr><td headers="hd_h_achm.T.allelic_disorders_not_in_the_diff_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>CNGB3</i>
|
|
</td><td headers="hd_h_achm.T.allelic_disorders_not_in_the_diff_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Macular degeneration</td><td headers="hd_h_achm.T.allelic_disorders_not_in_the_diff_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a class="bibr" href="#achm.REF.nishiguchi.2005.248" rid="achm.REF.nishiguchi.2005.248">Nishiguchi et al [2005]</a>
|
|
</td></tr><tr><td headers="hd_h_achm.T.allelic_disorders_not_in_the_diff_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>GNAT2</i>
|
|
</td><td headers="hd_h_achm.T.allelic_disorders_not_in_the_diff_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Oligo-cone trichromacy</td><td headers="hd_h_achm.T.allelic_disorders_not_in_the_diff_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a class="bibr" href="#achm.REF.rosenberg.2004.4256" rid="achm.REF.rosenberg.2004.4256">Rosenberg et al [2004]</a>
|
|
</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobachmTinheritedretinaldystrophiesto"><div id="achm.T.inherited_retinal_dystrophies_to" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Inherited Retinal Dystrophies to Consider in the Differential Diagnosis of Achromatopsia</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1418/table/achm.T.inherited_retinal_dystrophies_to/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__achm.T.inherited_retinal_dystrophies_to_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Overlapping Clinical Features</th><th id="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing Clinical Features</th><th id="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_6" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comments</th></tr></thead><tbody><tr><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Blue-cone monochromatism <sup>1</sup> (OMIM <a href="https://omim.org/entry/303700" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">303700</a>)</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>OPN1LW</i>; <i>OPN1MW</i> <sup>2</sup></td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL <sup>3</sup></td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Severely ↓ visual acuity</div></li><li class="half_rhythm"><div>Eccentric fixation</div></li><li class="half_rhythm"><div>± Infantile nystagmus</div></li><li class="half_rhythm"><div>No obvious fundus abnormalities</div></li><li class="half_rhythm"><div>Poor or no color discrimination <sup>4</sup></div></li></ul>
|
|
</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In blue-cone monochromatism:
|
|
<ul><li class="half_rhythm"><div>Peak of photopic luminosity function is near 440 nm (the peak sensitivity of the S cones), not 507 nm (the peak sensitivity of the rods).</div></li><li class="half_rhythm"><div>Mostly males are affected.</div></li></ul>
|
|
</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>A special 4-color plate test or a 2-color filter test can clinically distinguish blue-cone monochromats from achromats (rod monochromats).</div></li><li class="half_rhythm"><div>Cone ERG responses can be elicited by presenting blue flashes on a yellow background (because the S cones are functioning in addition to the rods).</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hereditary red-green color vision defects (OMIM <a href="https://omim.org/entry/303800" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">303800</a>, <a href="https://omim.org/entry/303900" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">303900</a>)</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>OPN1LW</i>, <i>OPN1MW</i></td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Color vision defects <sup>5</sup></td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In hereditary red-green color vision defects:
|
|
<ul><li class="half_rhythm"><div>Absence of ophthalmologic or other associated clinical abnormalities</div></li><li class="half_rhythm"><div>Most individuals w/protanomalous & deuteranomalous color vision defects (i.e., anomalous trichromats) have no major problems in naming colors.</div></li><li class="half_rhythm"><div>Mostly males are affected.</div></li></ul>
|
|
</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Clinical chart tests widely used to detect red-green color vision defects include Ishihara plates & the American Optical HRR pseudoisochromatic plates.</div></li><li class="half_rhythm"><div>Definitive classification of color vision defects known as protanopia, deuteranopia, protanomaly, & deuteranomaly requires use of anomaloscope, which involves color matching.</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Tritan and yellow-blue defects<br />(OMIM <a href="https://omim.org/entry/190900" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">190900</a>)</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>OPN1SW</i>
|
|
</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Color confusion</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<p>In tritan & yellow-blue defects: color confusion is limited to blues & greens. <sup>6</sup></p>
|
|
</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Other non-congenital yellow-blue deficits (similar in some ways to tritan defects) may result from aging or disorders of choroid, pigment epithelium, retina, or optic nerve (e.g., optic atrophy type 1; OMIM <a href="https://omim.org/entry/165500" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">165500</a>); they are usually progressive & have other related signs; e.g. associated visual acuity defects. <sup>7</sup></td></tr><tr><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cone / cone-rod dystrophies <sup>8</sup></td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>ABCA4</i>, <i>AIPL1</i>, <i>CABP4</i>, <i>CNNM4</i>, <i>CDHR1</i>, <i>GUCY2D</i>, <i>KCNV2</i>, <i>RAB28</i>, <i>RPGRIP1</i></td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD, AR</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Cone function may be normal at birth.</div></li><li class="half_rhythm"><div>Typical symptoms (↓ visual acuity, photophobia, ↑ sensitivity to glare, abnormal color vision) appear later. <sup>9</sup></div></li><li class="half_rhythm"><div>Age of onset of vision loss may be as early as childhood or as late as 7th decade.</div></li><li class="half_rhythm"><div>Dark-adapted rod thresholds may be elevated. <sup>10</sup></div></li></ul>
|
|
</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disease progression occurs in cone dystrophy & typically not in achromatopsia.</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Differentiating between achromatopsia & cone dystrophy can be difficult, particularly in individuals w/early-childhood onset.</div></li><li class="half_rhythm"><div>Best clinical discriminator is disease progression.</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/lca-ov/?report=reader">Leber congenital amaurosis</a> (LCA)</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>AIPL1</i>
|
|
<br />
|
|
<i>CABP4</i>
|
|
<br />
|
|
<i>CEP290</i>
|
|
<br />
|
|
<i>GUCY2D</i>
|
|
<br />
|
|
<i>RPGRIP1</i>
|
|
</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Infantile nystagmus</div></li><li class="half_rhythm"><div>Photophobia</div></li><li class="half_rhythm"><div>Severely reduced visual acuity</div></li><li class="half_rhythm"><div>No obvious fundus abnormalities</div></li><li class="half_rhythm"><div>Poor or no color discrimination</div></li></ul>
|
|
</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Night blindness & progression occur in LCA.</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In very young individuals</td></tr><tr><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Bradyopsia; delayed cone adaptation</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>RGS9</i>
|
|
</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Prolonged electroretinal response suppression leading to difficulties adjusting to changes in luminance</div></li><li class="half_rhythm"><div>Normal to subnormal visual acuity</div></li><li class="half_rhythm"><div>Photophobia</div></li></ul>
|
|
</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/alstrom/?report=reader">Alström syndrome</a> <sup>11</sup></td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>ALMS1</i>
|
|
</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Infantile nystagmus</div></li><li class="half_rhythm"><div>Photophobia</div></li><li class="half_rhythm"><div>Severely reduced visual acuity</div></li><li class="half_rhythm"><div>Poor or no color discrimination</div></li></ul>
|
|
</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Possible additional findings in Alström syndrome: cardiomyopathy, kidney failure, obesity, sensorineural hearing loss, diabetes</td><td headers="hd_h_achm.T.inherited_retinal_dystrophies_to_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In young individuals</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AD = autosomal dominant; AR = autosomal recessive; ERG = electroretinogram; MOI = mode of inheritance; XL = X-linked</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="achm.TF.3.1"><p class="no_margin">Blue-cone monochromacy may also be referred to as S-cone monochromacy or X-chromosome-linked achromatopsia.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="achm.TF.3.2"><p class="no_margin">The dysfunction of the L (red) and M (green) cones is caused by pathogenic variants leading to the loss of the X-linked red (<i>OPN1LW</i>) and green (<i>OPN1MW</i>) opsin gene array, hybrid gene formation and/or inactivating variants, or by deletions affecting the locus control region, a critical region that regulates the expression of the red/green (<i>OPN1LW/OPN1MW</i>) gene array.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="achm.TF.3.3"><p class="no_margin">Blue-cone monochromacy affects mostly males.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="achm.TF.3.4"><p class="no_margin">
|
|
<a class="bibr" href="#achm.REF.sharpe.1999" rid="achm.REF.sharpe.1999">Sharpe et al [1999]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="achm.TF.3.5"><p class="no_margin">Some males with mildly defective red-green color vision may not be aware of it until they are tested. Among individuals of northern European origin, about 8% of males and 0.5% of females have red-green color vision defects; these defects are less frequent among males of African (3%-4%) or Asian (3%) origin.</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="achm.TF.3.6"><p class="no_margin">Often referred to as yellow-blue disorders, although the color confusion is typically between blues & greens, tritan defects affect the S (blue) cones.</p></div></dd></dl><dl class="bkr_refwrap"><dt>7. </dt><dd><div id="achm.TF.3.7"><p class="no_margin">
|
|
<a class="bibr" href="#achm.REF.sharpe.1999" rid="achm.REF.sharpe.1999">Sharpe et al [1999]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>8. </dt><dd><div id="achm.TF.3.8"><p class="no_margin">See <a class="bibr" href="#achm.REF.gl_ckle.2014.99" rid="achm.REF.gl_ckle.2014.99">Glöckle et al [2014]</a>, <a class="bibr" href="#achm.REF.weisschuh.2016.e0145951" rid="achm.REF.weisschuh.2016.e0145951">Weisschuh et al [2016]</a>, <a class="bibr" href="#achm.REF.carss.2017.75" rid="achm.REF.carss.2017.75">Carss et al [2017]</a> for genes identified in patients misdiagnosed as having achromatopsia.</p></div></dd></dl><dl class="bkr_refwrap"><dt>9. </dt><dd><div id="achm.TF.3.9"><p class="no_margin">
|
|
<a class="bibr" href="#achm.REF.holopigian.2004.275" rid="achm.REF.holopigian.2004.275">Holopigian et al [2004]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>10. </dt><dd><div id="achm.TF.3.10"><p class="no_margin">
|
|
<a class="bibr" href="#achm.REF.aboshiha.2014.6340" rid="achm.REF.aboshiha.2014.6340">Aboshiha et al [2014]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>11. </dt><dd><div id="achm.TF.3.11"><p class="no_margin">
|
|
<a class="bibr" href="#achm.REF.nasser.2018.e445" rid="achm.REF.nasser.2018.e445">Nasser et al [2018]</a>
|
|
</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobachmmolgenTA"><div id="achm.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Achromatopsia: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1418/table/achm.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__achm.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_achm.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_achm.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_achm.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_achm.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_achm.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_achm.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_achm.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/22926" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>ATF6</i>
|
|
</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=22926" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">1q23<wbr style="display:inline-block"></wbr>​.3</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/P18850" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Cyclic AMP-dependent transcription factor ATF-6 alpha</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.lovd.nl/ATF6" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ATF6 @ LOVD</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=ATF6" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ATF6</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=ATF6[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ATF6</a>
|
|
</td></tr><tr><td headers="hd_b_achm.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/1261" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>CNGA3</i>
|
|
</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=1261" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">2q11<wbr style="display:inline-block"></wbr>​.2</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/Q16281" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Cyclic nucleotide-gated channel alpha-3</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.lovd.nl/CNGA3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CNGA3 @ LOVD</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=CNGA3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CNGA3</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=CNGA3[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CNGA3</a>
|
|
</td></tr><tr><td headers="hd_b_achm.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/54714" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>CNGB3</i>
|
|
</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=54714" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">8q21<wbr style="display:inline-block"></wbr>​.3</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/Q9NQW8" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Cyclic nucleotide-gated channel beta-3</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://databases.lovd.nl/shared/genes/CNGB3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CNGB3 @ LOVD</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=CNGB3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CNGB3</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=CNGB3[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CNGB3</a>
|
|
</td></tr><tr><td headers="hd_b_achm.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/2780" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>GNAT2</i>
|
|
</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=2780" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">1p13<wbr style="display:inline-block"></wbr>​.3</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/P19087" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Guanine nucleotide-binding protein G(t) subunit alpha-2</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;"></td><td headers="hd_b_achm.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=GNAT2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GNAT2</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=GNAT2[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GNAT2</a>
|
|
</td></tr><tr><td headers="hd_b_achm.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/5146" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>PDE6C</i>
|
|
</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=5146" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">10q23<wbr style="display:inline-block"></wbr>​.33</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/P51160" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha'</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://databases.lovd.nl/shared/genes/PDE6C" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDE6C @ LOVD</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=PDE6C" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDE6C</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=PDE6C[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDE6C</a>
|
|
</td></tr><tr><td headers="hd_b_achm.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/5149" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>PDE6H</i>
|
|
</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=5149" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">12p12<wbr style="display:inline-block"></wbr>​.3</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/Q13956" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Retinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://databases.lovd.nl/shared/genes/PDE6H" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDE6H @ LOVD</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=PDE6H" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDE6H</a>
|
|
</td><td headers="hd_b_achm.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=PDE6H[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDE6H</a>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div id="achm.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
|
|
<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
|
chromosome locus from
|
|
<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
|
protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
|
For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
|
<a href="/books/n/gene/app1/?report=reader">here</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobachmmolgenTB"><div id="achm.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Achromatopsia (<a href="/omim/139340,216900,262300,600053,600827,601190,605080,605537,610024,613093,613856,616517" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1418/table/achm.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__achm.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/139340" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">139340</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">GUANINE NUCLEOTIDE-BINDING PROTEIN, ALPHA-TRANSDUCING ACTIVITY POLYPEPTIDE 2; GNAT2</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/216900" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">216900</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ACHROMATOPSIA 2; ACHM2</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/262300" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">262300</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ACHROMATOPSIA 3; ACHM3</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/600053" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">600053</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CYCLIC NUCLEOTIDE-GATED CHANNEL, ALPHA-3; CNGA3</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/600827" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">600827</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">PHOSPHODIESTERASE 6C; PDE6C</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/601190" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">601190</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">PHOSPHODIESTERASE 6H; PDE6H</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/605080" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">605080</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CYCLIC NUCLEOTIDE-GATED CHANNEL, BETA-3; CNGB3</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/605537" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">605537</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ACTIVATING TRANSCRIPTION FACTOR 6; ATF6</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/610024" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">610024</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RETINAL CONE DYSTROPHY 3A; RCD3A</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/613093" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">613093</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CONE DYSTROPHY 4; COD4</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/613856" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">613856</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ACHROMATOPSIA 4; ACHM4</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/616517" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">616517</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ACHROMATOPSIA 7; ACHM7</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobachmTatf6pathogenicvariantsdiscusse"><div id="achm.T.atf6_pathogenic_variants_discusse" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p><i>ATF6</i> Pathogenic Variants Discussed in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1418/table/achm.T.atf6_pathogenic_variants_discusse/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__achm.T.atf6_pathogenic_variants_discusse_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_achm.T.atf6_pathogenic_variants_discusse_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_achm.T.atf6_pathogenic_variants_discusse_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_achm.T.atf6_pathogenic_variants_discusse_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th></tr></thead><tbody><tr><td headers="hd_h_achm.T.atf6_pathogenic_variants_discusse_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.970C>T</td><td headers="hd_h_achm.T.atf6_pathogenic_variants_discusse_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg324Cys</td><td headers="hd_h_achm.T.atf6_pathogenic_variants_discusse_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_007348.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_007348<wbr style="display:inline-block"></wbr>​.3</a>
|
|
<br />
|
|
<a href="https://www.ncbi.nlm.nih.gov/protein/NP_031374.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_031374<wbr style="display:inline-block"></wbr>​.2</a>
|
|
</td></tr><tr><td headers="hd_h_achm.T.atf6_pathogenic_variants_discusse_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1533+1G>C</td><td headers="hd_h_achm.T.atf6_pathogenic_variants_discusse_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 1.</td><td headers="hd_h_achm.T.atf6_pathogenic_variants_discusse_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_007348.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_007348<wbr style="display:inline-block"></wbr>​.3</a>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="achm.TF.4.1"><p class="no_margin">Two cDNAs were identified, one with partial intron retention and one with exon skipping [<a class="bibr" href="#achm.REF.kohl.2015.757" rid="achm.REF.kohl.2015.757">Kohl et al 2015</a>].</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobachmTcngb3pathogenicvariantsdiscuss"><div id="achm.T.cngb3_pathogenic_variants_discuss" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p><i>CNGB3</i> Pathogenic Variants Discussed in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1418/table/achm.T.cngb3_pathogenic_variants_discuss/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__achm.T.cngb3_pathogenic_variants_discuss_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_achm.T.cngb3_pathogenic_variants_discuss_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_achm.T.cngb3_pathogenic_variants_discuss_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_achm.T.cngb3_pathogenic_variants_discuss_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th></tr></thead><tbody><tr><td headers="hd_h_achm.T.cngb3_pathogenic_variants_discuss_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1148delC</td><td headers="hd_h_achm.T.cngb3_pathogenic_variants_discuss_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Thr383IlefsTer13</td><td headers="hd_h_achm.T.cngb3_pathogenic_variants_discuss_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_019098.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_019098<wbr style="display:inline-block"></wbr>​.3</a>
|
|
<br />
|
|
<a href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_061971.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_061971<wbr style="display:inline-block"></wbr>​.3</a>
|
|
</td></tr><tr><td headers="hd_h_achm.T.cngb3_pathogenic_variants_discuss_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1304C>T</td><td headers="hd_h_achm.T.cngb3_pathogenic_variants_discuss_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ser435Phe</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobachmTgnat2pathogenicvariantsdiscuss"><div id="achm.T.gnat2_pathogenic_variants_discuss" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p><i>GNAT2</i> Pathogenic Variants Discussed in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1418/table/achm.T.gnat2_pathogenic_variants_discuss/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__achm.T.gnat2_pathogenic_variants_discuss_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_achm.T.gnat2_pathogenic_variants_discuss_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_achm.T.gnat2_pathogenic_variants_discuss_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_achm.T.gnat2_pathogenic_variants_discuss_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th></tr></thead><tbody><tr><td headers="hd_h_achm.T.gnat2_pathogenic_variants_discuss_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.461+24G>A</td><td headers="hd_h_achm.T.gnat2_pathogenic_variants_discuss_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td><td headers="hd_h_achm.T.gnat2_pathogenic_variants_discuss_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001377295.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_001377295<wbr style="display:inline-block"></wbr>​.2</a>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobachmTpde6hpathogenicvariantsdiscuss"><div id="achm.T.pde6h_pathogenic_variants_discuss" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p><i>PDE6H</i> Pathogenic Variants Discussed in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1418/table/achm.T.pde6h_pathogenic_variants_discuss/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__achm.T.pde6h_pathogenic_variants_discuss_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_achm.T.pde6h_pathogenic_variants_discuss_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_achm.T.pde6h_pathogenic_variants_discuss_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_achm.T.pde6h_pathogenic_variants_discuss_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th></tr></thead><tbody><tr><td headers="hd_h_achm.T.pde6h_pathogenic_variants_discuss_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.35C>G</td><td headers="hd_h_achm.T.pde6h_pathogenic_variants_discuss_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ser12Ter</td><td headers="hd_h_achm.T.pde6h_pathogenic_variants_discuss_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_006205.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_006205<wbr style="display:inline-block"></wbr>​.2</a>
|
|
<br />
|
|
<a href="https://www.ncbi.nlm.nih.gov/protein/NP_006196.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_006196<wbr style="display:inline-block"></wbr>​.1</a>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></dl></div></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script></div></div>
|
|
|
|
|
|
|
|
|
|
<!-- Book content -->
|
|
|
|
<script type="text/javascript" src="/portal/portal3rc.fcgi/rlib/js/InstrumentNCBIBaseJS/InstrumentPageStarterJS.js"> </script>
|
|
|
|
|
|
<!-- CE8B5AF87C7FFCB1_0191SID /projects/books/PBooks@9.11 portal105 v4.1.r689238 Tue, Oct 22 2024 16:10:51 -->
|
|
<span id="portal-csrf-token" style="display:none" data-token="CE8B5AF87C7FFCB1_0191SID"></span>
|
|
|
|
<script type="text/javascript" src="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/js/3968615.js" snapshot="books"></script></body>
|
|
</html>
|