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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. </p></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK584551_"><span class="title" itemprop="name">Resources for Genetics Professionals — Genetic Disorders Associated with Founder Variants Common in the Georgian Jewish Population</span></h1><div class="contrib half_rhythm"><span itemprop="author">Stephanie E Wallace</span>, MD<div class="affiliation small">Senior Editor, <i>GeneReviews</i></div><div class="affiliation small">Clinical Professor, Department of Pediatrics<br />University of Washington<br />Seattle, Washington<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.wu@2rotide" class="oemail">ude.wu@2rotide</a></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">September 29, 2022</span>.</p><p><em>Estimated reading time: 1 minute</em></p></div><div class="body-content whole_rhythm" itemprop="text"><p>A founder variant is a pathogenic variant observed at high frequency in a specific population due to the presence of the variant in a single ancestor or small number of ancestors. The presence of a founder variant can affect the approach to molecular genetic testing. When one or more founder variants account for a large percentage of all pathogenic variants found in a population, testing for the founder variant(s) may be performed first.</p><p>The table below includes common founder variants – here defined as <b>three or fewer variants that account for >50% of the pathogenic variants identified in a single gene in individuals of a specific ancestry</b> – in individuals of Georgian Jewish ancestry. Note: Pathogenic variants that are common worldwide due to a DNA sequence hot spot are not considered founder variants and thus are not included.</p><div id="founder_georgian_jewish.T.genetic_disord" class="table"><h3><span class="label">Table. </span></h3><div class="caption"><p>Genetic Disorders Associated with Founder Variants Common in the Georgian Jewish Population</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK584551/table/founder_georgian_jewish.T.genetic_disord/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__founder_georgian_jewish.T.genetic_disord_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_6" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">% of Pathogenic Variants in Gene <sup>1</sup></th><th id="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_7" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Carrier Frequency</th><th id="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_8" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ethnicity</th><th id="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_9" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_10" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">References</th></tr></thead><tbody><tr><td headers="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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||
<i>ADA2</i>
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||
</td><td headers="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/ada2-def/">Adenosine deaminase 2 deficiency</a>
|
||
</td><td headers="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.139G>A</td><td headers="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gly47Arg</td><td headers="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~100% <sup>2</sup></td><td headers="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1/10</td><td headers="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Georgian Jewish</td><td headers="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_9" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001282225.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_001282225<wbr style="display:inline-block"></wbr>.2</a>
|
||
<br />
|
||
<a href="https://www.ncbi.nlm.nih.gov/protein/NP_001269154.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_001269154<wbr style="display:inline-block"></wbr>.1</a>
|
||
</td><td headers="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_10" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a class="bk_pop" href="#founder_georgian_jewish.REF.hashem.2017.70">Hashem et al [2017]</a>
|
||
</td></tr><tr><td headers="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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||
<i>CFTR</i>
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||
</td><td headers="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/cf/">Cystic fibrosis</a>
|
||
</td><td headers="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1075_1079delCAAACinsAAAAA</td><td headers="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gln359_Thr360delinsLysLys</td><td headers="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">70%</td><td headers="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1/26</td><td headers="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Georgian Jewish</td><td headers="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_9" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000492.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000492<wbr style="display:inline-block"></wbr>.4</a>
|
||
<br />
|
||
<a href="https://www.ncbi.nlm.nih.gov/protein/NP_000483.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000483<wbr style="display:inline-block"></wbr>.3</a>
|
||
</td><td headers="hd_h_founder_georgian_jewish.T.genetic_disord_1_1_1_10" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a class="bk_pop" href="#founder_georgian_jewish.REF.meizahav.2018.e41">Mei-Zahav et al [2018]</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">Included if ≤3 pathogenic variants account for ≥50% of variants identified in a specific ethnic group</p></div></dd><dt></dt><dd><div><p class="no_margin">AR = autosomal recessive; MOI = mode of inheritance</p></div></dd><dt>1. </dt><dd><div id="founder_georgian_jewish.TF.e.1"><p class="no_margin">Percentage does not account for the possibility of rare <i>de novo</i> pathogenic variants occurring in this population.</p></div></dd><dt>2. </dt><dd><div id="founder_georgian_jewish.TF.e.2"><p class="no_margin">To date, no additional pathogenic variants in this gene have been reported in individuals of this ethnicity.</p></div></dd></dl></div></div></div><div id="founder_georgian_jewish.References"><h2 id="_founder_georgian_jewish_References_">References</h2><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="founder_georgian_jewish.REF.hashem.2017.70">Hashem H, Kelly SJ, Ganson NJ, Hershfield MS. Deficiency of adenosine deaminase 2 (DADA2), an inherited cause of polyarteritis nodosa and a mimic of other systemic rheumatologic disorders. <span><span class="ref-journal">Curr Rheumatol Rep. </span>2017;<span class="ref-vol">19</span>:70.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28983775" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28983775</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="founder_georgian_jewish.REF.meizahav.2018.e41">Mei-Zahav M, Stafler P, Senderowitz H, Bentur L, Livnat G, Shteinberg M, Orenstein N, Bazak L, Prais D, Levine H, Gur M, Khazanov N, Simhaev L, Eliyahu H, Cohen M, Wilschanski M, Blau H, Mussaffi H. The Q359K/T360K mutation causes cystic fibrosis in Georgian Jews. <span><span class="ref-journal">J Cyst Fibros. </span>2018;<span class="ref-vol">17</span>:e41–e45.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/30033373" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30033373</span></a>]</div></li></ul></div><div id="founder_georgian_jewish.Revision_History"><h2 id="_founder_georgian_jewish_Revision_History_">Revision History</h2><ul><li class="half_rhythm"><div>29 September 2022 (sw) Initial posting</div></li></ul></div><div id="bk_toc_contnr"></div></div></div>
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