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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 class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="All GeneReviews" href="/books/n/gene/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-gene-lrg.png" alt="Cover of GeneReviews®" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>GeneReviews<sup>®</sup> [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK1230_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK1230_dtls__"><div>Adam MP, Feldman J, Mirzaa GM, et al., editors.</div><div>Seattle (WA): <a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>; 1993-2025.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/gene/">GeneReviews by Title</a></li></ul></div><div class="bk_noprnt"><form method="get" action="/books/n/gene/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search GeneReviews" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search GeneReviews" submit="false" style="padding: 0.1em 0.4em;" /></div></form><div><ul class="inline_list"><li><a href="/books/n/gene/advanced/">GeneReviews Advanced Search</a></li><li style="margin-left:.5em"><a href="/books/n/gene/helpadvsearch/">Help</a></li></ul></div></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/gene/pxe/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/pycnodys/" title="Next page in this title">Next ></a></div></div></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="_NBK1230_"><span class="title" itemprop="name">Pulmonary Fibrosis Predisposition Overview</span></h1><p class="contrib-group"><span itemprop="author">Christine Kim Garcia</span>, MD, PhD and <span itemprop="author">Janet L Talbert</span>, MS, CGC, LGC.</p><a data-jig="ncbitoggler" href="#__NBK1230_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK1230_ai__"><div class="contrib half_rhythm"><span itemprop="author">Christine Kim Garcia</span>, MD, PhD<div class="affiliation small">Columbia University Medical Center<br />New York, New York<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.aibmuloc.cmuc@6112gkc" class="oemail">ude.aibmuloc.cmuc@6112gkc</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Janet L Talbert</span>, MS, CGC, LGC<div class="affiliation small">Vanderbilt University Medical Center<br />Nashville, Tennessee<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="gro.cmuv@treblat.tenaj" class="oemail">gro.cmuv@treblat.tenaj</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">January 21, 2005</span>; Last Revision: <span itemprop="dateModified">May 12, 2022</span>.</p><p><em>Estimated reading time: 29 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="pf.Summary" itemprop="description"><h2 id="_pf_Summary_">Summary</h2><p>The purpose of this overview is to:</p><dl class="temp-labeled-list"><dt>1.</dt><dd><p class="no_top_margin">Briefly describe the <a href="#pf.Clinical_Characteristics_of_Pulmonary">clinical characteristics</a> of pulmonary fibrosis.</p></dd><dt>2.</dt><dd><p class="no_top_margin">Review genetic <a href="#pf.Genetic_Causes_of_Pulmonary_Fibrosis">causes</a> of pulmonary fibrosis.</p></dd><dt>3.</dt><dd><p class="no_top_margin">Review the <a href="#pf.Differential_Diagnosis_of_Pulmonary_F">differential diagnosis</a> of pulmonary fibrosis.</p></dd><dt>4.</dt><dd><p class="no_top_margin">Provide an <a href="#pf.Evaluation_Strategies_to_Identify_the">evaluation strategy</a> to identify the genetic cause of pulmonary fibrosis in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</p></dd><dt>5.</dt><dd><p class="no_top_margin">Review <a href="#pf.Management_of_Pulmonary_Fibrosis">management</a> of pulmonary fibrosis.</p></dd><dt>6.</dt><dd><p class="no_top_margin">Inform <a href="#pf.Genetic_Counseling">genetic counseling</a> of family members of an individual with a genetic predisposition to pulmonary fibrosis.</p></dd></dl>
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</div><div id="pf.Clinical_Characteristics_of_Pulmonary"><h2 id="_pf_Clinical_Characteristics_of_Pulmonary_">1. Clinical Characteristics of Pulmonary Fibrosis</h2><div id="pf.Clinical_Features_of_Pulmonary_Fibros"><h3>Clinical Features of Pulmonary Fibrosis</h3><p>Individuals with pulmonary fibrosis typically present with shortness of breath with exertion and a dry cough. Disease onset during adulthood is most common, but onset can range over multiple decades. Most individuals with pulmonary fibrosis have had a history of smoking or fibrogenic environmental exposures [<a class="bk_pop" href="#pf.REF.borie.2016.1721">Borie et al 2016</a>, <a class="bk_pop" href="#pf.REF.newton.2016.1710">Newton et al 2016</a>, <a class="bk_pop" href="#pf.REF.salisbury.2020.1230">Salisbury et al 2020</a>]. The prevalence of fibrotic lung disease increases with age.</p><p>Dry rales are identified on pulmonary auscultation. Hypoxemia with exertion is usually one of the earliest signs. With disease progression, hypoxemia occurs at rest. Symptoms worsen over time as lung scarring progresses. Later findings include finger clubbing, signs of pulmonary hypertension, and sequelae of right heart failure.</p><p>Degradation of pulmonary function occurs over time, with progressive decline of forced vital capacity and diffusion capacity. Most individuals die of respiratory causes. Transplant-free survival appears to be lower for individuals with <i>TERC</i> or <i>TERT</i> pathogenic variants than for those without identifiable pathogenic variants in these two genes [<a class="bk_pop" href="#pf.REF.borie.2016.1721">Borie et al 2016</a>].</p></div><div id="pf.Radiographic_Features_of_Pulmonary_Fi"><h3>Radiographic Features of Pulmonary Fibrosis</h3><p>The distribution and extent of specific radiographic features of pulmonary fibrosis can vary, but generally pulmonary fibrosis is characterized by reticulations, traction bronchiectasis, and honeycombing. Individual interstitial lung diseases are associated with different radiographic patterns and features. Radiographic patterns of lung involvement in individuals with certain pathogenic variants may be atypical (see <a href="/books/NBK1230/table/pf.T.predisposition_to_pulmonary_fibrosi/?report=objectonly" target="object" rid-ob="figobpfTpredispositiontopulmonaryfibrosi">Table 1</a>).</p></div></div><div id="pf.Genetic_Causes_of_Pulmonary_Fibrosis"><h2 id="_pf_Genetic_Causes_of_Pulmonary_Fibrosis_">2. Genetic Causes of Pulmonary Fibrosis</h2><div id="pf.Suggestive_Features_of_a_Genetic_Caus"><h3>Suggestive Features of a Genetic Cause of Pulmonary Fibrosis</h3><p>The presence of a genetic cause of predisposition to pulmonary fibrosis can be suggested by family history or by clinical features of a known genetic cause of pulmonary fibrosis (see <a href="/books/NBK1230/table/pf.T.predisposition_to_pulmonary_fibrosi/?report=objectonly" target="object" rid-ob="figobpfTpredispositiontopulmonaryfibrosi">Table 1</a> and <a href="/books/NBK1230/table/pf.T.syndromes_in_which_pulmonary_fibros/?report=objectonly" target="object" rid-ob="figobpfTsyndromesinwhichpulmonaryfibros">Table 2</a>).</p><p><b>Family history.</b> Familial pulmonary fibrosis (FPF) describes the occurrence of fibrotic interstitial lung disease (ILD) in at least two related family members. The specific ILD diagnosis may vary in affected individuals from the same family [<a class="bk_pop" href="#pf.REF.lee.2012.1577">Lee et al 2012</a>, <a class="bk_pop" href="#pf.REF.newton.2016.1710">Newton et al 2016</a>]. Individuals with FPF may be clinically diagnosed with any of the following disorders:</p><ul><li class="half_rhythm"><div>Idiopathic pulmonary fibrosis (~50% of individuals with FPF) [<a class="bk_pop" href="#pf.REF.borie.2016.1721">Borie et al 2016</a>, <a class="bk_pop" href="#pf.REF.newton.2016.1710">Newton et al 2016</a>]</div></li><li class="half_rhythm"><div>Chronic hypersensitivity pneumonitis (~10% of individuals with FPF) [<a class="bk_pop" href="#pf.REF.okamoto.2013.384">Okamoto et al 2013</a>, <a class="bk_pop" href="#pf.REF.borie.2016.1721">Borie et al 2016</a>, <a class="bk_pop" href="#pf.REF.newton.2016.1710">Newton et al 2016</a>]</div></li><li class="half_rhythm"><div>Progressive pulmonary fibrosis [<a class="bk_pop" href="#pf.REF.newton.2016.1710">Newton et al 2016</a>]</div></li><li class="half_rhythm"><div>Idiopathic interstitial pneumonia (IIP) (e.g., unclassifiable IIP, nonspecific interstitial pneumonia, pleuroparenchymal fibroelastosis, among others) [<a class="bk_pop" href="#pf.REF.reddy.2012.377">Reddy et al 2012</a>, <a class="bk_pop" href="#pf.REF.borie.2016.1721">Borie et al 2016</a>, <a class="bk_pop" href="#pf.REF.newton.2016.1710">Newton et al 2016</a>, <a class="bk_pop" href="#pf.REF.nunes.2017.1602022">Nunes et al 2017</a>]</div></li><li class="half_rhythm"><div>Connective tissue disease-associated ILD, including rheumatoid arthritis ILD and scleroderma ILD [<a class="bk_pop" href="#pf.REF.juge.2017.1602314">Juge et al 2017</a>]</div></li><li class="half_rhythm"><div>Drug-induced ILD [<a class="bk_pop" href="#pf.REF.borie.2016.1721">Borie et al 2016</a>]</div></li><li class="half_rhythm"><div>Pulmonary fibrosis and adenocarcinoma of the lung</div></li><li class="half_rhythm"><div>Combined pulmonary fibrosis and emphysema [<a class="bk_pop" href="#pf.REF.nunes.2014.753">Nunes et al 2014</a>, <a class="bk_pop" href="#pf.REF.stanley.2015.563">Stanley et al 2015</a>, <a class="bk_pop" href="#pf.REF.stanley.2016.351ra107">Stanley et al 2016</a>]</div></li></ul><p><b>Adenocarcinoma of the lung.</b> Individuals with <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> pulmonary fibrosis are at a threefold greater risk of developing adenocarcinoma of the lung compared to the general population [<a class="bk_pop" href="#pf.REF.yoon.2018.195">Yoon et al 2018</a>]. A variant of non-small cell lung cancer previously described as bronchoalveolar cancer, arising from the alveolar acinar epithelial with a lepidic growth pattern in the presence or absence of minimally invasive disease, suggests an <i>SFTPA1</i> or <i>SFTPA2</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> [<a class="bk_pop" href="#pf.REF.wang.2009.52">Wang et al 2009</a>, <a class="bk_pop" href="#pf.REF.van_moorsel.2015.1249">van Moorsel et al 2015</a>, <a class="bk_pop" href="#pf.REF.nathan.2016.1457">Nathan et al 2016</a>].</p><p><b>Clinical features of a short telomere syndrome</b> (e.g., <a href="/books/n/gene/dkc/">dyskeratosis congenita</a>) include skin reticular pigmentation, nail dystrophy, oral mucosal leukoplakia, premature graying of hair (age <30 years), thrombocytopenia, macrocytosis, aplastic anemia, bone marrow failure, immunodeficiency, myelodysplasia, acute leukemia, elevated liver enzymes, liver cirrhosis, gastrointestinal disease, radiation sensitivity, and infertility [<a class="bk_pop" href="#pf.REF.newton.2016.1710">Newton et al 2016</a>]. Hepatopulmonary syndrome and the development of pulmonary fibrosis after liver transplantation have been reported in individuals with short telomere syndrome [<a class="bk_pop" href="#pf.REF.gorgy.2015.1019">Gorgy et al 2015</a>]. Features of short telomere syndrome are more common in individuals with pathogenic variants in <i>DKC1</i>, <i>TINF2</i>, and <i>TERC</i> than <i>TERT</i>, <i>RTEL1</i>, or <i>PARN</i>.</p></div><div id="pf.Prognosis_for_Those_with_a_Predisposi"><h3>Prognosis for Those with a Predisposition to Pulmonary Fibrosis</h3><p>Median survival for those with <i>TERT</i>- or <i>TERC</i>-related pulmonary fibrosis was 3.7 years in a European cohort; this was shorter than the life expectancy of the entire cohort of individuals with a suspected genetic cause of pulmonary fibrosis (6.3 years) [<a class="bk_pop" href="#pf.REF.borie.2016.1721">Borie et al 2016</a>]. Median life expectancy for a United States cohort with pulmonary fibrosis due to pathogenic variants in <i>TERT, TERC, RTEL1,</i> and <i>PARN</i> was 2.9 years.</p></div><div id="pf.Influence_of_Environmental_Exposures"><h3>Influence of Environmental Exposures</h3><p>Cigarette smoking and exposures to inhaled agents are frequently reported by individuals with an identified genetic predisposition to pulmonary fibrosis, suggesting that the combination of genetic predisposition and environmental exposures are particularly injurious [<a class="bk_pop" href="#pf.REF.diaz_de_leon.2010.e10680">Diaz de Leon et al 2010</a>, <a class="bk_pop" href="#pf.REF.borie.2016.1721">Borie et al 2016</a>, <a class="bk_pop" href="#pf.REF.newton.2016.1710">Newton et al 2016</a>, <a class="bk_pop" href="#pf.REF.salisbury.2020.1230">Salisbury et al 2020</a>].</p></div><div id="pf.Pulmonary_Fibrosis__Associated_Genes"><h3>Pulmonary Fibrosis – Associated Genes and Syndromes</h3><p>See <a href="/books/NBK1230/table/pf.T.predisposition_to_pulmonary_fibrosi/?report=objectonly" target="object" rid-ob="figobpfTpredispositiontopulmonaryfibrosi">Table 1</a> and <a href="/books/NBK1230/table/pf.T.syndromes_in_which_pulmonary_fibros/?report=objectonly" target="object" rid-ob="figobpfTsyndromesinwhichpulmonaryfibros">Table 2</a>.</p><div id="pf.T.predisposition_to_pulmonary_fibrosi" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Predisposition to Pulmonary Fibrosis: Genes and Distinguishing Clinical Features</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1230/table/pf.T.predisposition_to_pulmonary_fibrosi/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__pf.T.predisposition_to_pulmonary_fibrosi_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></th><th id="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">% of all FPF</th><th id="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Age of Onset of Pulmonary Fibrosis</th><th id="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_6" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing Features</th></tr></thead><tbody><tr><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_1" rowspan="8" scope="rowgroup" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Genes associated w/telomere maintenance <sup>2</sup></b>
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</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>DKC1</i>
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</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~1% <sup>3</sup></td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL <sup>4</sup></td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Adult</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Short telomere syndrome features</td></tr><tr><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>NAF1</i>
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</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~1% <sup>5, 6</sup></td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Adult</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Combined PF & emphysema; short telomere syndrome features</td></tr><tr><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>PARN</i>
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</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4%-5% <sup>5, 7</sup></td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD<br />AR</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mean: 64 yrs</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>RTEL1</i>
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</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4%-9% <sup>5, 8</sup></td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mean: 60 yrs</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>TERC</i>
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</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2%-5% <sup>9</sup></td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mean: 51 yrs</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Short telomere syndrome features</td></tr><tr><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>TERT</i>
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</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">15%-20% <sup>5, 10, 11</sup></td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>40 yrs (mean: 58 yrs; PF in >60% of those age >60 yrs)</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Some persons have combined PF & emphysema</td></tr><tr><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>TINF2</i>
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</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~1% <sup>12</sup></td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Adult</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Short telomere syndrome features</td></tr><tr><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>ZCCHC8</i>
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</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><1%</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Adult</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">± bone marrow failure</td></tr><tr><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_1" rowspan="4" scope="rowgroup" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Genes associated w/surfactant metabolism</b>
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</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ABCA3</i>
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</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><1% <sup>13</sup></td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare in adults, more common in childhood-onset PF</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Lung radiographs show ground glass opacities, reticulations, & cysts of variable size, predominantly involving upper lobes</td></tr><tr><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>SFTPA1</i>
|
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</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><1% <sup>14, 15</sup></td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Adult</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Lung adenocarcinoma</td></tr><tr><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>SFTPA2</i>
|
||
</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><1% <sup>14, 16</sup></td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Adult</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Lung adenocarcinoma</td></tr><tr><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>SFTPC</i>
|
||
</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1%-5% <sup>14, 17</sup></td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infancy to late adulthood</td><td headers="hd_h_pf.T.predisposition_to_pulmonary_fibrosi_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Wide array of radiographic abnormalities, incl combined PF & emphysema, & atypical upper lobe involvement <sup>18</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">AD = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a>; AR = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a>; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; PF = pulmonary fibrosis</p></div></dd><dt>1. </dt><dd><div id="pf.TF.1.1"><p class="no_margin">Genes are listed alphabetically.</p></div></dd><dt>2. </dt><dd><div id="pf.TF.1.2"><p class="no_margin">Persons w/predisposition to PF associated with a <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> involved in telomere maintenance may have additional features within the spectrum of telomere biology disorders (of which classic <a href="/books/n/gene/dkc/">dyskeratosis congenita</a> is the most severe <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>; see <a href="/books/NBK1230/table/pf.T.syndromes_in_which_pulmonary_fibros/?report=objectonly" target="object" rid-ob="figobpfTsyndromesinwhichpulmonaryfibros">Table 2</a>).</p></div></dd><dt>3. </dt><dd><div id="pf.TF.1.3"><p class="no_margin"><a class="bk_pop" href="#pf.REF.alder.2013.1481">Alder et al [2013]</a>, <a class="bk_pop" href="#pf.REF.kropski.2014.e1">Kropski et al [2014]</a></p></div></dd><dt>4. </dt><dd><div id="pf.TF.1.4"><p class="no_margin">Heterozygous females can be variably affected [<a class="bk_pop" href="#pf.REF.alder.2013.1481">Alder et al 2013</a>].</p></div></dd><dt>5. </dt><dd><div id="pf.TF.1.5"><p class="no_margin">Loss-of-function variants in <i>NAF1, PARN, RTEL1,</i> and <i>TERT</i> are typically pathogenic.</p></div></dd><dt>6. </dt><dd><div id="pf.TF.1.6"><p class="no_margin">
|
||
<a class="bk_pop" href="#pf.REF.stanley.2016.351ra107">Stanley et al [2016]</a>
|
||
</p></div></dd><dt>7. </dt><dd><div id="pf.TF.1.7"><p class="no_margin">OMIM <a href="https://omim.org/entry/616371" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">616371</a>; rarely associated with AR inheritance [<a class="bk_pop" href="#pf.REF.zhang.2019.797">Zhang et al 2019</a>]</p></div></dd><dt>8. </dt><dd><div id="pf.TF.1.8"><p class="no_margin">OMIM <a href="https://omim.org/entry/616373" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">616373</a></p></div></dd><dt>9. </dt><dd><div id="pf.TF.1.9"><p class="no_margin">OMIM <a href="https://omim.org/entry/614743" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">614743</a></p></div></dd><dt>10. </dt><dd><div id="pf.TF.1.10"><p class="no_margin">OMIM <a href="https://omim.org/entry/614742" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">614742</a></p></div></dd><dt>11. </dt><dd><div id="pf.TF.1.11"><p class="no_margin">Individuals with <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> pathogenic variants in genes associated with short telomere syndrome, especially those older than age 60 years, may acquire somatic <i>TERT</i> promoter pathogenic variants in circulating leukocytes [<a class="bk_pop" href="#pf.REF.maryoung.2017.982">Maryoung et al 2017</a>, <a class="bk_pop" href="#pf.REF.gutierrezrodrigues.2019.1594">Gutierrez-Rodrigues et al 2019</a>].</p></div></dd><dt>12. </dt><dd><div id="pf.TF.1.12"><p class="no_margin">
|
||
<a class="bk_pop" href="#pf.REF.alder.2015.1361">Alder et al [2015]</a>
|
||
</p></div></dd><dt>13. </dt><dd><div id="pf.TF.1.13"><p class="no_margin">OMIM <a href="https://omim.org/entry/610921" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">610921</a>; <a class="bk_pop" href="#pf.REF.campo.2014.43">Campo et al [2014]</a>, <a class="bk_pop" href="#pf.REF.epaud.2014.638">Epaud et al [2014]</a></p></div></dd><dt>14. </dt><dd><div id="pf.TF.1.14"><p class="no_margin">Pathogenic variants in the surfactant metabolism genes (<i>SFTPA1</i>, <i>SFTPA2</i>, <i>SFTPC</i>) are typically <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a> variants that lead to increased endoplasmic reticulum stress.</p></div></dd><dt>15. </dt><dd><div id="pf.TF.1.15"><p class="no_margin">
|
||
<a class="bk_pop" href="#pf.REF.nathan.2016.1457">Nathan et al [2016]</a>
|
||
</p></div></dd><dt>16. </dt><dd><div id="pf.TF.1.16"><p class="no_margin">OMIM <a href="https://omim.org/entry/178642" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">178642</a></p></div></dd><dt>17. </dt><dd><div id="pf.TF.1.17"><p class="no_margin">OMIM <a href="https://omim.org/entry/610913" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">610913</a></p></div></dd><dt>18. </dt><dd><div id="pf.TF.1.18"><p class="no_margin"><a class="bk_pop" href="#pf.REF.mechri.2010.1021">Mechri et al [2010]</a>, <a class="bk_pop" href="#pf.REF.van_moorsel.2010.1419">van Moorsel et al [2010]</a></p></div></dd></dl></div></div></div><div id="pf.T.syndromes_in_which_pulmonary_fibros" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Syndromes in which Pulmonary Fibrosis is a Common Feature: Genes and Distinguishing Clinical Features</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1230/table/pf.T.syndromes_in_which_pulmonary_fibros/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__pf.T.syndromes_in_which_pulmonary_fibros_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_pf.T.syndromes_in_which_pulmonary_fibros_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_pf.T.syndromes_in_which_pulmonary_fibros_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_pf.T.syndromes_in_which_pulmonary_fibros_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_pf.T.syndromes_in_which_pulmonary_fibros_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Pulmonary Phenotype</th><th id="hd_h_pf.T.syndromes_in_which_pulmonary_fibros_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Other Clinical & Laboratory Features</th></tr></thead><tbody><tr><td headers="hd_h_pf.T.syndromes_in_which_pulmonary_fibros_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>ACD</i>
|
||
<br />
|
||
<i>CTC1</i>
|
||
<br />
|
||
<i>DKC1</i>
|
||
<br />
|
||
<i>NAF1</i>
|
||
<br />
|
||
<i>NHP2</i>
|
||
<br />
|
||
<i>NOP10</i>
|
||
<br />
|
||
<i>PARN</i>
|
||
<br />
|
||
<i>RTEL1</i>
|
||
<br />
|
||
<i>STN1</i>
|
||
<br />
|
||
<i>TERC</i>
|
||
<br />
|
||
<i>TERT</i>
|
||
<br />
|
||
<i>TINF2</i>
|
||
<br />
|
||
<i>WRAP53</i>
|
||
<br />
|
||
<i>ZCCHC8</i>
|
||
</td><td headers="hd_h_pf.T.syndromes_in_which_pulmonary_fibros_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/dkc/">Dyskeratosis congenita and related telomere biology disorders</a> (DC/TBD)</td><td headers="hd_h_pf.T.syndromes_in_which_pulmonary_fibros_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL<br />AR<br />AD</td><td headers="hd_h_pf.T.syndromes_in_which_pulmonary_fibros_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PF may be a presenting sign or may develop over time. Note: Some genes assoc w/DC may cause PF w/o other features of DC (see <a href="/books/NBK1230/table/pf.T.predisposition_to_pulmonary_fibrosi/?report=objectonly" target="object" rid-ob="figobpfTpredispositiontopulmonaryfibrosi">Table 1</a>).</td><td headers="hd_h_pf.T.syndromes_in_which_pulmonary_fibros_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Variable: skin reticular pigmentation, nail dystrophy, oral mucosal leukoplakia, premature graying of hair, bone marrow failure, myelodysplastic syndrome, acute myelogenous leukemia, liver cirrhosis, immunodeficiency, gastrointestinal disease, radiation sensitivity, infertility, shortened telomere length</td></tr><tr><td headers="hd_h_pf.T.syndromes_in_which_pulmonary_fibros_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>AP3B1</i><br /><i>HPS1</i><br /><i>HPS4</i> <sup>1</sup></td><td headers="hd_h_pf.T.syndromes_in_which_pulmonary_fibros_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/hps/">Hermansky-Pudlak syndrome</a> (HPS)</td><td headers="hd_h_pf.T.syndromes_in_which_pulmonary_fibros_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_pf.T.syndromes_in_which_pulmonary_fibros_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Onset of PF is typically in 4th decade & fatal w/in 10 yrs; PF is most common in <i>HPS1</i>-related HPS.</td><td headers="hd_h_pf.T.syndromes_in_which_pulmonary_fibros_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Tyrosinase-positive oculocutaneous albinism; bleeding diathesis resulting from a platelet storage pool deficiency</td></tr><tr><td headers="hd_h_pf.T.syndromes_in_which_pulmonary_fibros_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>FAM111B</i>
|
||
</td><td headers="hd_h_pf.T.syndromes_in_which_pulmonary_fibros_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/hfpoik-tmp/">Hereditary fibrosing poikiloderma w/tendon contractures, myopathy, & pulmonary fibrosis</a>
|
||
</td><td headers="hd_h_pf.T.syndromes_in_which_pulmonary_fibros_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_pf.T.syndromes_in_which_pulmonary_fibros_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">± adult-onset progressive PF, can be life threatening</td><td headers="hd_h_pf.T.syndromes_in_which_pulmonary_fibros_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early-onset poikiloderma, hypotrichosis, hypohidrosis, mild lymphedema, multiple contractures, myopathy, scoliosis, exocrine pancreatic insufficiency, liver impairment, hematologic abnormalities</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">AD = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a>; AR = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a>; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; PF = pulmonary fibrosis; XL = <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a></p></div></dd><dt>1. </dt><dd><div id="pf.TF.2.1"><p class="no_margin">To date, convincing evidence of pulmonary fibrosis has not been reported in affected individuals with pathogenic variants in other HPS-related genes.</p></div></dd></dl></div></div></div></div></div><div id="pf.Differential_Diagnosis_of_Pulmonary_F"><h2 id="_pf_Differential_Diagnosis_of_Pulmonary_F_">3. Differential Diagnosis of Pulmonary Fibrosis</h2><p>
|
||
<b>Acquired (non-genetic) causes of pulmonary fibrosis</b>
|
||
</p><ul><li class="half_rhythm"><div>Fibrogenic environmental exposures, including smoking, radiation, asbestosis, inhaled metal and fine inorganic particulates, coal, bird antigens and droppings, certain organic dusts</div></li><li class="half_rhythm"><div>Inflammation, such as arising from respiratory infections</div></li><li class="half_rhythm"><div>Associated with other medical conditions (sarcoidosis, rheumatoid arthritis, scleroderma, dermatomyositis, connective tissue disorders, immunodeficiency, and others)</div></li><li class="half_rhythm"><div>Medications, especially chemotherapy and antiarrhythmia medications</div></li></ul><p>Other <b>genetic disorders</b> that exhibit diffuse parenchymal lung disease as a clinical feature are summarized in <a href="/books/NBK1230/table/pf.T.inherited_disorders_that_exhibit_di/?report=objectonly" target="object" rid-ob="figobpfTinheriteddisordersthatexhibitdi">Table 3</a>.</p><div id="pf.T.inherited_disorders_that_exhibit_di" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Inherited Disorders that Exhibit Diffuse Parenchymal Lung Disease as a Clinical Feature</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1230/table/pf.T.inherited_disorders_that_exhibit_di/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__pf.T.inherited_disorders_that_exhibit_di_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Pulmonary Phenotype</th><th id="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Other Clinical & Laboratory Features</th></tr></thead><tbody><tr><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>CFTR</i>
|
||
</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_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_pf.T.inherited_disorders_that_exhibit_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Progressive obstructive lung disease, bronchiectasis, recurrent pulmonary infections, PF, respiratory failure</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Pancreatic insufficiency, malnutrition, recurrent sinusitis & bronchitis, male infertility, meconium ileus</td></tr><tr><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>COPA</i>
|
||
</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Autoimmune interstitial lung, joint, & kidney disease (OMIM <a href="https://omim.org/entry/616414" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">616414</a>)</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Affects children & young adults; lymphocytic lung infiltrates</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">High-titer autoantibodies, inflammatory arthritis, kidney disease</td></tr><tr><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>GBA1</i><br />(<i>GBA</i>)</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/gaucher/">Gaucher disease type 1</a>
|
||
</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><5% w/interstitial lung involvement characterized by infiltration of Gaucher cells</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood presentation of hepatosplenomegaly, pancytopenia, & bone disease</td></tr><tr><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>NF1</i>
|
||
</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/nf1/">Neurofibromatosis 1</a>
|
||
</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">± adult-onset parenchymal lung disease (bullae ± interstitial fibrosis) often in assoc w/pulmonary hypertension</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Multiple café au lait macules, axillary & inguinal freckling, cutaneous neurofibromas, Lisch nodules, plexiform neurofibromas, ID</td></tr><tr><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>NKX2-1</i>
|
||
</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Brain-lung-thyroid syndrome (See <a href="/books/n/gene/nkx2-1-dis/"><i>NKX2-1</i>-Related Disorders</a>.)</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infant respiratory distress is common w/recurrent pulmonary infections, chronic ILD, respiratory failure</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Choreoathetosis & <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> hypothyroidism</td></tr><tr><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>RNF168</i>
|
||
</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">RIDDLE syndrome (OMIM <a href="https://omim.org/entry/611943" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">611943</a>)</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Radiation sensitivity, PF</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Immunodeficiency, ID, <a class="def" href="/books/n/gene/glossary/def-item/dysmorphic/">dysmorphic</a> features, short stature</td></tr><tr><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>SMPD1</i>
|
||
</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Niemann-Pick disease type B (See <a href="/books/n/gene/npab/">Acid Sphingomyelinase Deficiency</a>.)</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Most affected persons develop widespread ILD, recurrent lung infections, respiratory failure</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hepatosplenomegaly w/progressive hypersplenism & stable liver dysfunction; atherogenic lipid profile</td></tr><tr><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>TMEM173</i>
|
||
</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">STING-associated vasculopathy (OMIM <a href="https://omim.org/entry/615934" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">615934</a>)</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infantile or childhood-onset ILD</td><td headers="hd_h_pf.T.inherited_disorders_that_exhibit_di_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Autoinflammatory vasculopathy, severe ulcerative skin lesions (face, ears, nose, digits), arthritis, autoantibodies, immune complex deposition</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">AD = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a>; AR = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a>; ID = intellectual disability; ILD = interstitial lung disease; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; PF = pulmonary fibrosis</p></div></dd></dl></div></div></div></div><div id="pf.Evaluation_Strategies_to_Identify_the"><h2 id="_pf_Evaluation_Strategies_to_Identify_the_">4. Evaluation Strategies to Identify the Genetic Cause of Pulmonary Fibrosis in a Proband</h2><p>Establishing a specific genetic cause of pulmonary fibrosis:</p><ul><li class="half_rhythm"><div>Can aid in discussions of prognosis (which are beyond the scope of this <i>GeneReview</i>) and <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a>;</div></li><li class="half_rhythm"><div>Usually involves a medical history, physical examination, family history, pulmonary function testing, imaging, lung biopsy, and <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a>.</div></li></ul><p>
|
||
<b>Medical history</b>
|
||
</p><ul><li class="half_rhythm"><div><b>Age of onset.</b> Onset of pulmonary fibrosis in childhood or adults younger than age 30 years suggests an <i>SFTPC</i> or <i>ABCA3</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> (a surfactant metabolism disorder).</div></li><li class="half_rhythm"><div><b>Evaluate for features of a short telomere syndrome</b> (e.g., <a href="/books/n/gene/dkc/">dyskeratosis congenita</a>; see <a href="/books/NBK1230/table/pf.T.syndromes_in_which_pulmonary_fibros/?report=objectonly" target="object" rid-ob="figobpfTsyndromesinwhichpulmonaryfibros">Table 2</a>), including premature graying of hair (often diffuse and before age 30 years), oral cancer, bone marrow failure, myelodysplasia, acute leukemia, aplastic anemia, leukopenia, macrocytosis, thrombocytopenia, avascular necrosis/osteoporosis, liver cirrhosis, elevated liver enzymes, immunodeficiency, radiation sensitivity, and infertility.</div></li></ul><p><b>Physical examination.</b> Physical features of a <b>short telomere syndrome</b> (e.g., dyskeratosis congenita; see <a href="/books/NBK1230/table/pf.T.syndromes_in_which_pulmonary_fibros/?report=objectonly" target="object" rid-ob="figobpfTsyndromesinwhichpulmonaryfibros">Table 2</a>) include dermal reticular pigmentation, nail dystrophy, oral mucosal leukoplakia, and premature graying of the hair.</p><p><b>Family history.</b> A three-generation family history should be taken, with attention to relatives with features of pulmonary fibrosis, age of onset, clinical features of a short telomere syndrome, evidence of <a class="def" href="/books/n/gene/glossary/def-item/anticipation/">anticipation</a> suggestive of a short telomere syndrome (see <a href="#pf.Related_Genetic_Counseling_Issues">Related Genetic Counseling Issues</a>, <b>Anticipation</b>), evidence of <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> inheritance (<i>DKC1</i> should be considered if all affected individuals are males younger than age 50 years), and documentation of relevant findings through direct examination or review of medical records, including results of <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a>.</p><p><b>Laboratory features.</b> Shortened telomere length is seen in blood leukocytes measured by flow cytometry with <a class="def" href="/books/n/gene/glossary/def-item/fluorescent-in-situ-hybridization/">fluorescent in situ hybridization</a> (flow <a class="def" href="/books/n/gene/glossary/def-item/fish/">FISH</a>).</p><p>Note: (1) Telomere length measurement should be offered to individuals with pulmonary fibrosis and extrapulmonary manifestations of a short telomere syndrome (e.g., dyskeratosis congenita; see <a href="/books/NBK1230/table/pf.T.syndromes_in_which_pulmonary_fibros/?report=objectonly" target="object" rid-ob="figobpfTsyndromesinwhichpulmonaryfibros">Table 2</a>). (2) This testing may be useful to help establish a diagnosis in individuals with inconclusive results on <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a>.</p><ul><li class="half_rhythm"><div>If the age-adjusted neutrophil or lymphocyte telomere length is <10th percentile, <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> of genes associated with a short telomere syndrome should be considered (see <a href="/books/NBK1230/table/pf.T.syndromes_in_which_pulmonary_fibros/?report=objectonly" target="object" rid-ob="figobpfTsyndromesinwhichpulmonaryfibros">Table 2</a>) [<a class="bk_pop" href="#pf.REF.diaz_de_leon.2010.e10680">Diaz de Leon et al 2010</a>, <a class="bk_pop" href="#pf.REF.snetselaar.2015.1011">Snetselaar et al 2015</a>].</div></li><li class="half_rhythm"><div>If the age-adjusted neutrophil or lymphocyte telomere length is >10th percentile, panels that include surfactant metabolism genes (<i>SFTPC</i>, <i>SFTPA1</i>, <i>SFTPA2)</i> or other genetic syndromes (see <a href="/books/NBK1230/table/pf.T.predisposition_to_pulmonary_fibrosi/?report=objectonly" target="object" rid-ob="figobpfTpredispositiontopulmonaryfibrosi">Table 1</a> and <a href="/books/NBK1230/table/pf.T.syndromes_in_which_pulmonary_fibros/?report=objectonly" target="object" rid-ob="figobpfTsyndromesinwhichpulmonaryfibros">Table 2</a>) should be considered.</div></li><li class="half_rhythm"><div>Note: Shortened telomeres can be inherited independently of the associated <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> and result in a clinical phenocopy of the short telomere syndrome in offspring who do not inherit the associated pathogenic variant [<a class="bk_pop" href="#pf.REF.alder.2011.e1001352">Alder et al 2011</a>] (see <a href="#pf.Related_Genetic_Counseling_Issues">Related Genetic Counseling Issues</a>).</div></li></ul><p><b>Molecular genetic testing.</b> A <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a> is recommended [<a class="bk_pop" href="#pf.REF.borie.2017.160122">Borie et al 2017</a>, <a class="bk_pop" href="#pf.REF.kropski.2017.1423">Kropski et al 2017</a>]. Sequence analysis should be performed first<i>.</i> If no <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> is found, <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> can be considered, although large deletions/duplications have not been reported.</p><ul><li class="half_rhythm"><div><i>SFTPC</i> and <i>ABCA3</i> should be included if disease onset is before age 30 years or if there is a wide range in age among affected individuals in the family.</div></li><li class="half_rhythm"><div>Panels that include genes associated with a short telomere syndrome (e.g., dyskeratosis congenita; see <a href="/books/NBK1230/table/pf.T.syndromes_in_which_pulmonary_fibros/?report=objectonly" target="object" rid-ob="figobpfTsyndromesinwhichpulmonaryfibros">Table 2</a>) should be included when clinical and/or laboratory features of a short telomere syndrome are present.</div></li><li class="half_rhythm"><div>Panels should include <i>SFTPA1</i> and <i>SFTPA2</i> if there is a personal or family history of adenocarcinoma of the lung, especially non-small cell lung cancer (previously described as bronchoalveolar cancer), arising from the alveolar acinar epithelial with a lepidic growth pattern in the presence or absence of minimally invasive disease.</div></li><li class="half_rhythm"><div>Additional <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> panels should be considered if there is overlap with clinical features associated with related disorders (see <a href="/books/NBK1230/table/pf.T.inherited_disorders_that_exhibit_di/?report=objectonly" target="object" rid-ob="figobpfTinheriteddisordersthatexhibitdi">Table 3</a>).</div></li></ul><p>For an introduction to multigene panels click <a href="/books/n/gene/app5/#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/#app5.Multigene_Panels_FAQs">here</a>.</p></div><div id="pf.Management_of_Pulmonary_Fibrosis"><h2 id="_pf_Management_of_Pulmonary_Fibrosis_">5. Management of Pulmonary Fibrosis</h2><div id="pf.Evaluations_Following_Initial_Diagnos"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with a predisposition to pulmonary fibrosis, the evaluations summarized in <a href="/books/NBK1230/table/pf.T.recommended_evaluations_following_i/?report=objectonly" target="object" rid-ob="figobpfTrecommendedevaluationsfollowingi">Table 4</a> (if not performed as part of the evaluation that led to the diagnosis) should be considered.</p><div id="pf.T.recommended_evaluations_following_i" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with Predisposition to Pulmonary Fibrosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1230/table/pf.T.recommended_evaluations_following_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__pf.T.recommended_evaluations_following_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_pf.T.recommended_evaluations_following_i_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_pf.T.recommended_evaluations_following_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_pf.T.recommended_evaluations_following_i_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_pf.T.recommended_evaluations_following_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Pulmonary</b>
|
||
<br />
|
||
<b>fibrosis</b>
|
||
</td><td headers="hd_h_pf.T.recommended_evaluations_following_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Clinical history & exam for comorbidities</div></li><li class="half_rhythm"><div>Chest radiograph</div></li><li class="half_rhythm"><div>HRCT scan of chest</div></li><li class="half_rhythm"><div>Pulmonary function studies</div></li><li class="half_rhythm"><div>Eval by pulmonologist, preferably one w/experience in PF</div></li></ul>
|
||
</td><td headers="hd_h_pf.T.recommended_evaluations_following_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comorbidities that may affect disease course (e.g., pulmonary hypertension, obstructive sleep apnea, emphysema, GERD, & obesity)</td></tr><tr><td headers="hd_h_pf.T.recommended_evaluations_following_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Dyskeratosis</b>
|
||
<br />
|
||
<b>congenita <sup>1</sup></b>
|
||
</td><td headers="hd_h_pf.T.recommended_evaluations_following_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See Dyskeratosis Congenita and Related Telomere Biology Disorders, <a href="/books/n/gene/dkc/#dkc.Evaluations_Following_Initial_Diagno">Evaluations Following Initial Diagnosis</a>.</td><td headers="hd_h_pf.T.recommended_evaluations_following_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_pf.T.recommended_evaluations_following_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Genetic</b>
|
||
<br />
|
||
<b>counseling</b>
|
||
</td><td headers="hd_h_pf.T.recommended_evaluations_following_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>2</sup></td><td headers="hd_h_pf.T.recommended_evaluations_following_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To obtain a <a class="def" href="/books/n/gene/glossary/def-item/pedigree/">pedigree</a> & inform affected persons & families re nature, MOI, & implications of FPF to facilitate medical & personal decision making</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">FPF = <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> pulmonary fibrosis; GERD = gastroesophageal reflux disease; HRCT = high-resolution computed tomography; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; PF = pulmonary fibrosis</p></div></dd><dt>1. </dt><dd><div id="pf.TF.4.1"><p class="no_margin">Most often associated with pathogenic variants in <i>TERC</i> or <i>TERT</i></p></div></dd><dt>2. </dt><dd><div id="pf.TF.4.2"><p class="no_margin">Clinical geneticist, certified genetic counselor, certified genetic nurse, genetics advanced practice provider (nurse practitioner or physician assistant)</p></div></dd></dl></div></div></div></div><div id="pf.Treatment"><h3>Treatment</h3><p>Clinical management of pulmonary fibrosis due to a genetic cause is similar to that for individuals with other causes of fibrotic interstitial lung disease and depends on the subtype of interstitial lung disease. It is recommended that individuals be evaluated by a pulmonologist, preferably one with experience in treating <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> pulmonary fibrosis.</p><div id="pf.T.treatment_of_manifestations_in_indi" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with Predisposition to Pulmonary Fibrosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1230/table/pf.T.treatment_of_manifestations_in_indi/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__pf.T.treatment_of_manifestations_in_indi_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_pf.T.treatment_of_manifestations_in_indi_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_pf.T.treatment_of_manifestations_in_indi_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_pf.T.treatment_of_manifestations_in_indi_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_pf.T.treatment_of_manifestations_in_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Idiopathic PF</b>
|
||
</td><td headers="hd_h_pf.T.treatment_of_manifestations_in_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Antifibrotic medications <sup>1</sup><br />(nintedanib, <sup>2</sup> pirfenidone <sup>3</sup>)</td><td headers="hd_h_pf.T.treatment_of_manifestations_in_indi_1_1_1_3" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">Monitoring of side effects</td></tr><tr><td headers="hd_h_pf.T.treatment_of_manifestations_in_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Progressive PF</b>
|
||
</td><td headers="hd_h_pf.T.treatment_of_manifestations_in_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Nintedanib <sup>4</sup></td></tr><tr><td headers="hd_h_pf.T.treatment_of_manifestations_in_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Unclassifiable</b>
|
||
<br />
|
||
<b>progressive PF</b>
|
||
</td><td headers="hd_h_pf.T.treatment_of_manifestations_in_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Pirfenidone <sup>5</sup></td></tr><tr><td headers="hd_h_pf.T.treatment_of_manifestations_in_indi_1_1_1_1" rowspan="4" scope="rowgroup" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Any progressive PF</b>
|
||
</td><td headers="hd_h_pf.T.treatment_of_manifestations_in_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consideration of lung transplantation:
|
||
<ul><li class="half_rhythm"><div>In persons w/primarily lung limitations & few manifestations of other organ failure</div></li><li class="half_rhythm"><div>Often an option because most persons w/hereditary PF are age <70 yrs</div></li></ul>
|
||
</td><td headers="hd_h_pf.T.treatment_of_manifestations_in_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In persons w/short telomere:
|
||
<ul><li class="half_rhythm"><div>Adjustment of immunosuppressive medication may be required to avoid drug toxicities in those w/hematologic abnormalities. <sup>6</sup></div></li><li class="half_rhythm"><div>Subclinical bone marrow abnormalities may affect immunosuppression at time of lung transplantation. <sup>7</sup></div></li><li class="half_rhythm"><div>Cytomegalovirus-related morbidity after lung transplantation has been reported. <sup>8</sup></div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_pf.T.treatment_of_manifestations_in_indi_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Oxygen</td><td headers="hd_h_pf.T.treatment_of_manifestations_in_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">May improve exercise tolerance & prevent or delay onset of pulmonary hypertension & right heart failure</td></tr><tr><td headers="hd_h_pf.T.treatment_of_manifestations_in_indi_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Treatment of comorbid conditions</td><td headers="hd_h_pf.T.treatment_of_manifestations_in_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Eval (as clinically indicated) & treatment of pulmonary embolism, lung cancer, pulmonary hypertension, GERD, obstructive sleep apnea</td></tr><tr><td headers="hd_h_pf.T.treatment_of_manifestations_in_indi_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Pulmonary rehab</td><td headers="hd_h_pf.T.treatment_of_manifestations_in_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">May improve exercise tolerance</td></tr><tr><td headers="hd_h_pf.T.treatment_of_manifestations_in_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Short telomere</b>
|
||
<br />
|
||
<b>syndrome</b>
|
||
</td><td headers="hd_h_pf.T.treatment_of_manifestations_in_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See Dyskeratosis Congenita and Related Telomere Biology Disorders, <a href="/books/n/gene/dkc/#dkc.Treatment_of_Manifestations">Treatment of Manifestations</a>.</td><td headers="hd_h_pf.T.treatment_of_manifestations_in_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">GERD = gastroesophageal reflux disease; PF = pulmonary fibrosis</p></div></dd><dt>1. </dt><dd><div id="pf.TF.5.1"><p class="no_margin">Treatment with antifibrotic medications (e.g., nintedanib, pirfenidone), was associated with an improved trajectory in lung function (i.e., less forced vital capacity decline) in individuals with short telomere-related pathogenic variants. A European study did not find a difference between the two medications in terms of efficacy [<a class="bk_pop" href="#pf.REF.justet.2021.2003198">Justet et al 2021</a>]. A US study found that individuals taking pirfenidone had less lung function decline, regardless of the degree of telomere shortening [<a class="bk_pop" href="#pf.REF.dressen.2018.603">Dressen et al 2018</a>].</p></div></dd><dt>2. </dt><dd><div id="pf.TF.5.2"><p class="no_margin">
|
||
<a class="bk_pop" href="#pf.REF.richeldi.2014.2071">Richeldi et al [2014]</a>
|
||
</p></div></dd><dt>3. </dt><dd><div id="pf.TF.5.3"><p class="no_margin">
|
||
<a class="bk_pop" href="#pf.REF.king.2014.2083">King et al [2014]</a>
|
||
</p></div></dd><dt>4. </dt><dd><div id="pf.TF.5.4"><p class="no_margin">
|
||
<a class="bk_pop" href="#pf.REF.flaherty.2019.1718">Flaherty et al [2019]</a>
|
||
</p></div></dd><dt>5. </dt><dd><div id="pf.TF.5.5"><p class="no_margin">
|
||
<a class="bk_pop" href="#pf.REF.maher.2020.147">Maher et al [2020]</a>
|
||
</p></div></dd><dt>6. </dt><dd><div id="pf.TF.5.6"><p class="no_margin"><a class="bk_pop" href="#pf.REF.silhan.2014.178">Silhan et al [2014]</a>, <a class="bk_pop" href="#pf.REF.borie.2015.538">Borie et al [2015]</a>, <a class="bk_pop" href="#pf.REF.tokman.2015.1318">Tokman et al [2015]</a></p></div></dd><dt>7. </dt><dd><div id="pf.TF.5.7"><p class="no_margin">
|
||
<a class="bk_pop" href="#pf.REF.george.2015.1549">George et al [2015]</a>
|
||
</p></div></dd><dt>8. </dt><dd><div id="pf.TF.5.8"><p class="no_margin">
|
||
<a class="bk_pop" href="#pf.REF.popescu.2019.362">Popescu et al [2019]</a>
|
||
</p></div></dd></dl></div></div></div></div><div id="pf.Surveillance"><h3>Surveillance</h3><div id="pf.T.recommended_surveillance_for_indivi" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with Predisposition to Pulmonary Fibrosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1230/table/pf.T.recommended_surveillance_for_indivi/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__pf.T.recommended_surveillance_for_indivi_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_pf.T.recommended_surveillance_for_indivi_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_pf.T.recommended_surveillance_for_indivi_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_pf.T.recommended_surveillance_for_indivi_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_pf.T.recommended_surveillance_for_indivi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Pulmonary</b>
|
||
<br />
|
||
<b>fibrosis</b>
|
||
</td><td headers="hd_h_pf.T.recommended_surveillance_for_indivi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>PFTs: spirometry (incl FVC), plethysmography, & DLCO</div></li><li class="half_rhythm"><div>High-resolution chest CT</div></li><li class="half_rhythm"><div>Oxygen saturation by pulse oximetry at rest & w/exertion (exercise-related hypoxemia precedes development of hypoxemia at rest)</div></li><li class="half_rhythm"><div>6-MWT distance & oxygen saturation measurements</div></li></ul>
|
||
</td><td headers="hd_h_pf.T.recommended_surveillance_for_indivi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">The frequency of surveillance has not been established. It is common to obtain baseline testing at age ~40 yrs. Those w/features of early disease need frequent follow up (every 3-12 mos) to determine durability & progression of findings. Those w/no evidence of early disease could have less frequent repeat testing. Since early initiation of antifibrotic therapeutics is recommended, surveillance testing at regular intervals is strongly recommended. Repeat PFTs, oxygen desaturation studies, & 6-MWT incur less radiation exposure than repeat chest CTs.</td></tr><tr><td headers="hd_h_pf.T.recommended_surveillance_for_indivi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Dyskeratosis</b>
|
||
<br />
|
||
<b>congenita</b>
|
||
</td><td headers="hd_h_pf.T.recommended_surveillance_for_indivi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See Dyskeratosis Congenita and Related Telomere Biology Disorders, <a href="/books/n/gene/dkc/#dkc.Surveillance">Surveillance</a>.</td><td headers="hd_h_pf.T.recommended_surveillance_for_indivi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">6-MWT = six-minute walk test; DLCO = diffusion capacity of the lung for carbon monoxide; FVC = forced vital capacity; PFT = pulmonary function test</p></div></dd></dl></div></div></div></div><div id="pf.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p><b>Environmental exposures.</b> Every effort should be made to remove and avoid environmental exposures linked to the development of pulmonary fibrosis. Deleterious environmental exposures include but are not limited to: smoking, metal fumes/dust, wood dust, stone and sand particulates, certain agricultural, farming and livestock exposures, bird feather and droppings, aerosolized molds, as well as certain medications including chemotherapeutics, antiarrhythmia agents, and nitrofurantoin.</p></div><div id="pf.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>It is appropriate to evaluate apparently asymptomatic older and younger first-degree relatives of an affected individual in order to identify as early as possible those who would benefit from avoidance of environmental risks and initiation of antifibrotic medications to slow down the rate of progression of disease in those with early findings of lung fibrosis. Evaluations can include the following:</p><ul><li class="half_rhythm"><div>Molecular genetic testing if a molecular diagnosis has been established in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></div></li><li class="half_rhythm"><div>If a molecular diagnosis has not been established in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> but there is a family history of pulmonary fibrosis, the following evaluations are recommended:</div><ul><li class="half_rhythm"><div>Baseline high-resolution chest CT and PFTs for all individuals at age 40 years or ten years before the earliest diagnosis in affected family members</div></li><li class="half_rhythm"><div>If any abnormality is discovered in a <a class="def" href="/books/n/gene/glossary/def-item/first-degree-relative/">first-degree relative</a>, it is recommended that testing be repeated to determine the durability and progression of findings. Although the frequency of testing has not been established, it is the author's clinical practice to repeat pulmonary function tests (PFTs), oxygen desaturation studies, or six-minute walk testing (6-MWT) every three to 12 months. Frequency of testing depends on symptoms and trend. Repeat PFTs, oxygen desaturation studies, and 6-MWT incur less radiation exposure than repeat chest CTs (see <a href="/books/NBK1230/table/pf.T.recommended_surveillance_for_indivi/?report=objectonly" target="object" rid-ob="figobpfTrecommendedsurveillanceforindivi">Table 6</a>).</div></li><li class="half_rhythm"><div>Telomere length testing can be considered, especially if there is a personal or family history to suggest a short telomere syndrome.</div></li></ul></li></ul><p><b>Environmental exposures.</b> Development and progression of interstitial lung abnormalities in family members have been associated with environmental exposures. Progression of radiographic abnormalities occurred in most individuals who had detectable early radiographic abnormalities [<a class="bk_pop" href="#pf.REF.salisbury.2020.1230">Salisbury et al 2020</a>].</p><p>Every effort should be made to remove and avoid environmental exposures linked to the development of pulmonary fibrosis. Deleterious environmental exposures include but are not limited to: smoking, metal fumes/dust, wood dust, stone and sand particulates, certain agricultural, farming and livestock exposures, bird feather and droppings, aerosolized molds, as well as certain medications including chemotherapeutics, antiarrhythmia agents, and nitrofurantoin.</p><p><b>Note:</b> It is recommended that individuals with a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>(s) in a <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> associated with telomere maintenance (see <a href="/books/NBK1230/table/pf.T.predisposition_to_pulmonary_fibrosi/?report=objectonly" target="object" rid-ob="figobpfTpredispositiontopulmonaryfibrosi">Table 1</a>) and their families undergo <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> with a healthcare provider who has experience with monogenic short telomere syndromes and related complications (see <a href="#pf.Related_Genetic_Counseling_Issues">Related Genetic Counseling Issues</a>).</p></div><div id="pf.Therapies_under_Investigation"><h3>Therapies under Investigation</h3><p>Many therapies are under investigation for the treatment of pulmonary fibrosis. 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 access to information on clinical studies for a wide range of diseases and conditions.</p></div></div><div id="pf.Genetic_Counseling"><h2 id="_pf_Genetic_Counseling_">6. 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="pf.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Almost all <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> pathogenic variants known to be associated with predisposition to pulmonary fibrosis (see <a href="/books/NBK1230/table/pf.T.predisposition_to_pulmonary_fibrosi/?report=objectonly" target="object" rid-ob="figobpfTpredispositiontopulmonaryfibrosi">Table 1</a>) are associated with <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> inheritance. Less commonly, predisposition to pulmonary fibrosis is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner (<i>ABCA3</i>-related pulmonary fibrosis) or an <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> manner (<i>DKC1</i>-related pulmonary fibrosis).</p><p>Genetic counseling for pulmonary fibrosis associated with a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>(s) in a <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> involved in telomere maintenance (see <a href="/books/NBK1230/table/pf.T.predisposition_to_pulmonary_fibrosi/?report=objectonly" target="object" rid-ob="figobpfTpredispositiontopulmonaryfibrosi">Table 1</a>) may be complicated by factors such as <a class="def" href="/books/n/gene/glossary/def-item/anticipation/">anticipation</a> and clinical phenocopies (see <a href="#pf.Related_Genetic_Counseling_Issues">Related Genetic Counseling Issues</a>); it is recommended that individuals and their families undergo <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> with a healthcare provider who has experience with monogenic short telomere syndromes.</p><p>Note: Individuals with <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> pathogenic variants in genes associated with short telomere syndrome, especially those older than age 60 years, may acquire somatic <i>TERT</i> promoter pathogenic variants in circulating leukocytes [<a class="bk_pop" href="#pf.REF.maryoung.2017.982">Maryoung et al 2017</a>, <a class="bk_pop" href="#pf.REF.gutierrezrodrigues.2019.1594">Gutierrez-Rodrigues et al 2019</a>]. Somatic <i>TERT</i> promoter pathogenic variants are not transmitted to offspring.</p><p><b>Syndromic pulmonary fibrosis.</b> If a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> has <a class="def" href="/books/n/gene/glossary/def-item/syndromic/">syndromic</a> pulmonary fibrosis (e.g., <a href="/books/n/gene/dkc/">dyskeratosis congenita</a> or features suggestive of a syndrome listed in <a href="/books/NBK1230/table/pf.T.syndromes_in_which_pulmonary_fibros/?report=objectonly" target="object" rid-ob="figobpfTsyndromesinwhichpulmonaryfibros">Table 2</a>), <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> for the specific syndrome is appropriate.</p></div><div id="pf.Autosomal_Dominant_Inheritance__Risk"><h3>Autosomal Dominant Inheritance – Risk to Family Members</h3><p>
|
||
<b>Parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>Some individuals diagnosed with predisposition to pulmonary fibrosis inherited a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> from an affected parent. Because some genetic causes of pulmonary fibrosis can be associated with <a class="def" href="/books/n/gene/glossary/def-item/anticipation/">anticipation</a>, an affected parent may have a later age of onset than the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</div></li><li class="half_rhythm"><div>Alternatively, a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with predisposition to pulmonary fibrosis may have a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>. The overall proportion of individuals with predisposition to pulmonary fibrosis caused by a <i>de novo</i> pathogenic variant is unknown.</div></li><li class="half_rhythm"><div>If a molecular diagnosis has been established in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>, <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> is recommended for both parents to ascertain their genetic status and to allow reliable <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> counseling. (Note: Because individuals with predisposition to pulmonary fibrosis are often diagnosed late in the adult years, parental genetic testing is not feasible in many families.)</div></li><li class="half_rhythm"><div>If the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> is not identified in either parent, the following possibilities should be considered:</div><ul><li class="half_rhythm"><div>The <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> has a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>. Note: A pathogenic variant is reported as "<i>de novo</i>" if: (1) the pathogenic variant found in the proband is not detected in parental DNA; and (2) parental identity testing has confirmed biological maternity and paternity. If parental identity testing is not performed, the variant is reported as "assumed <i>de novo</i>" [<a class="bk_pop" href="#pf.REF.richards.2015.405">Richards et al 2015</a>].</div></li><li class="half_rhythm"><div>The <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> inherited a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> from a parent with <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> (or somatic and germline) <a class="def" href="/books/n/gene/glossary/def-item/mosaicism/">mosaicism</a>. Note: Testing of parental leukocyte DNA may not detect all instances of <a class="def" href="/books/n/gene/glossary/def-item/somatic-mosaicism/">somatic mosaicism</a> and will not detect a pathogenic variant that is present in the germ cells only.</div></li></ul></li><li class="half_rhythm"><div>The family history of some individuals diagnosed with predisposition to pulmonary fibrosis may appear to be negative because of failure to recognize the disorder in affected family members (due to lack of appropriate radiographic imaging) and/or reduced, age-related <a class="def" href="/books/n/gene/glossary/def-item/penetrance/">penetrance</a> (i.e., late onset of the disease in the affected parent or early death of the parent before onset of symptoms). Therefore, an apparently negative family history cannot be confirmed without appropriate clinical evaluation (including radiographic imaging) of the parents and/or <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (to establish that neither parent is <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>).</div></li></ul><p><b>Sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> The risk to the sibs of the proband depends on the genetic status of the proband's parents:</p><ul><li class="half_rhythm"><div>If a parent of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> is affected or is known to have a pulmonary fibrosis-related <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, the risk to the sibs of inheriting the pulmonary fibrosis-related pathogenic variant is 50%. Because predisposition to pulmonary fibrosis is associated with reduced <a class="def" href="/books/n/gene/glossary/def-item/penetrance/">penetrance</a> and intrafamilial clinical variability, the age of onset and clinical manifestations in a sib who inherits a <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> pathogenic variant cannot be predicted.</div></li><li class="half_rhythm"><div>In families segregating a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in a <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> associated with telomere maintenance (see <a href="/books/NBK1230/table/pf.T.predisposition_to_pulmonary_fibrosi/?report=objectonly" target="object" rid-ob="figobpfTpredispositiontopulmonaryfibrosi">Table 1</a>), sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> are at risk of inheriting the <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> pathogenic variant and are at risk for <a class="def" href="/books/n/gene/glossary/def-item/epigenetic/">epigenetic</a> inheritance of shortened telomere length. The inheritance of shortened telomere length (with or without the familial pathogenic variant) can result in manifestations of a short telomere syndrome (including pulmonary fibrosis) (see <a href="#pf.Related_Genetic_Counseling_Issues">Related Genetic Counseling Issues</a>).</div></li><li class="half_rhythm"><div>If the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> has a known pulmonary fibrosis <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> that cannot be detected in the leukocyte DNA of either parent, the <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> to sibs is estimated to be 1% because of the theoretic possibility of parental <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a> [<a class="bk_pop" href="#pf.REF.rahbari.2016.126">Rahbari et al 2016</a>].</div></li></ul><p><b>Offspring of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> Each child of an individual with a <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> associated with predisposition to pulmonary fibrosis has a 50% chance of inheriting the pathogenic variant.</p><p><b>Other family members.</b> The risk to other family members depends on their biological relationship with the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> and the genetic status of the proband’s parents.</p></div><div id="pf.Autosomal_Recessive_Inheritance__Risk"><h3>Autosomal Recessive Inheritance – Risk to Family Members</h3><p>
|
||
<b>Parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>The parents of an affected individual are obligate heterozygotes (i.e., presumed to be carriers of one <i>ABCA3</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> based on family history).</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> to confirm that both parents are <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for one <i>ABCA3</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> and to allow reliable <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> assessment. If a pathogenic variant is detected in only one parent, the following possibilities should be considered:</div><ul><li class="half_rhythm"><div>One of the pathogenic variants identified in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> occurred as a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> event in the proband or as a <a class="def" href="/books/n/gene/glossary/def-item/postzygotic/">postzygotic</a> <i>de novo</i> event in a mosaic parent [<a class="bk_pop" href="#pf.REF.j_nsson.2017.519">Jónsson et al 2017</a>].</div></li><li class="half_rhythm"><div>Uniparental isodisomy for the parental <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> with the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> resulted in homozygosity for the pathogenic variant in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</div></li></ul></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 <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>If both parents are known to be <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for an <i>ABCA3</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a>, 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 <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> The offspring of an individual with <i>ABCA3</i>-related nonsyndromic pulmonary fibrosis are obligate heterozygotes (carriers) for a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>ABCA3</i>.</p><p><b>Other family members.</b> Each sib of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>'s parents is at a 50% risk of being a <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> of a <i>ABCA3</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</p><p><b>Carrier detection.</b> Carrier testing for at-risk relatives requires prior identification of the <i>ABCA3</i> pathogenic variants in the family.</p></div><div id="pf.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>See Management of Pulmonary Fibrosis, <a href="#pf.Evaluation_of_Relatives_at_Risk">Evaluation of Relatives at Risk</a> for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment</p><p><b>Genetic counseling for short telomere syndrome.</b> It is recommended that individuals with a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>(s) in a <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> associated with telomere maintenance (see <a href="/books/NBK1230/table/pf.T.predisposition_to_pulmonary_fibrosi/?report=objectonly" target="object" rid-ob="figobpfTpredispositiontopulmonaryfibrosi">Table 1</a>) and their families undergo <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> with a healthcare provider who has experience with monogenic short telomere syndromes and complicating factors including the following:</p><ul><li class="half_rhythm"><div><b>Epigenetic inheritance.</b> Shortened telomere length is transmitted from parent to offspring independently of the <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> short telomere syndrome-causing <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> (i.e., the offspring of a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> individual may inherit shortened telomere length but not the pathogenic variant).</div></li><li class="half_rhythm"><div><b>Clinical phenocopies.</b> An individual who inherits a shortened telomere length but not the <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> may have manifestations of a short telomere syndrome (i.e., a clinical phenocopy) because of <a class="def" href="/books/n/gene/glossary/def-item/epigenetic/">epigenetic</a> inheritance of shortened telomere length [<a class="bk_pop" href="#pf.REF.alder.2011.e1001352">Alder et al 2011</a>]. Consequently, assessment of <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> based on family history (rather than <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> and telomere length measurement) is unreliable.</div></li><li class="half_rhythm"><div><b>Anticipation.</b> Anticipation (the occurrence of increasing disease severity and decreasing age of onset in successive generations) may be observed in pulmonary fibrosis caused by a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>(s) in a <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> associated with telomere maintenance (see <a href="/books/NBK1230/table/pf.T.predisposition_to_pulmonary_fibrosi/?report=objectonly" target="object" rid-ob="figobpfTpredispositiontopulmonaryfibrosi">Table 1</a>). This phenomenon is the result of <a class="def" href="/books/n/gene/glossary/def-item/epigenetic/">epigenetic</a> transmission of progressively shorter telomere lengths in conjunction with <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> transmission of the <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> pathogenic variant (i.e., offspring of an affected individual who inherit both the familial pathogenic variant and a shorter telomere length than that in their transmitting parent) [<a class="bk_pop" href="#pf.REF.armanios.2005.15960">Armanios et al 2005</a>, <a class="bk_pop" href="#pf.REF.armanios.2009.45">Armanios 2009</a>, <a class="bk_pop" href="#pf.REF.newton.2016.1710">Newton et al 2016</a>, <a class="bk_pop" href="#pf.REF.borie.2017.160122">Borie et al 2017</a>].</div></li><li class="half_rhythm"><div><b>Variant interpretation.</b> The lack of cosegregation of a <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> genetic variant and clinical manifestations (resulting from <a class="def" href="/books/n/gene/glossary/def-item/epigenetic/">epigenetic</a> inheritance and phenocopies) raises the possibility that the variant is not pathogenic (see <a href="#pf.Evaluation_Strategies_to_Identify_the">Evaluation Strategies to Identify the Genetic Cause of Pulmonary Fibrosis in a Proband</a>, <b>Molecular genetic testing</b>).</div></li></ul><p>
|
||
<b>Family planning</b>
|
||
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/<a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk.</div></li></ul><p><b>DNA banking.</b> Because it is likely that testing methodology and our understanding of genes, pathogenic mechanisms, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative pathogenic mechanism is unknown). For more information, see <a class="bk_pop" href="#pf.REF.huang.2022.389">Huang et al [2022]</a>.</p></div><div id="pf.Prenatal_Testing_and_Preimplantation"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the pulmonary fibrosis-causing <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> has been identified in an affected family member, prenatal and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> are possible. Note: Age of onset, severity of disease, specific symptoms, and rate of disease progression are variable and cannot be accurately predicted by the family history or prenatal <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a>.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a>. While most health care professionals would consider use of prenatal and preimplantation genetic testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="pf.Resources"><h2 id="_pf_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/">here</a>.</i></p>
|
||
<ul><li class="half_rhythm"><div>
|
||
<b>American Lung Association</b>
|
||
</div><div>55 West Wacker Drive</div><div>Suite 1150</div><div>Chicago IL 60601</div><div><b>Phone:</b> 1-800-LUNGUSA</div><div>
|
||
<a href="http://www.lung.org/lung-disease/pulmonary-fibrosis/understanding-pulmonary.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Understanding Pulmonary Fibrosis</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>American Thoracic Society Patient Information Series</b>
|
||
</div><div>
|
||
<a href="https://www.thoracic.org/patients/lung-disease-week/2020/pf-week/general-info.php" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">General Information About Pulmonary Fibrosis</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>MedlinePlus</b>
|
||
</div><div>
|
||
<a href="https://medlineplus.gov/genetics/condition/idiopathic-pulmonary-fibrosis/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Idiopathic pulmonary fibrosis (IPF)</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>National Heart, Lung, and Blood Institute</b>
|
||
</div><div>
|
||
<a href="http://www.nhlbi.nih.gov/health/health-topics/topics/ipf/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Idiopathic Pulmonary Fibrosis (IPF)</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Pulmonary Fibrosis Foundation</b>
|
||
</div><div>230 East Ohio Street</div><div>Suite 500</div><div>Chicago IL 60611</div><div><b>Phone:</b> 844-825-5733 (toll-free)</div><div><b>Fax:</b> 866-587-9158 (toll-free)</div><div><b>Email:</b> info@pulmonaryfibrosis.org</div><div>
|
||
<a href="http://www.pulmonaryfibrosis.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.pulmonaryfibrosis.org</a>
|
||
</div></li></ul>
|
||
</div><div id="pf.Chapter_Notes"><h2 id="_pf_Chapter_Notes_">Chapter Notes</h2><div id="pf.Author_Notes"><h3>Author Notes</h3><p>Dr Garcia is the Frode-Jensen Professor of Medicine at Columbia University Irving Medical Center, as well as the Chief of the Division of Pulmonary, Allergy, and Critical Care Medicine, and the Acting Director of the Interstitial Lung Disease Program. She obtained her MD and PhD degrees, as well as completed residency in Internal Medicine and fellowship in Pulmonary and Critical Care Medicine, at the University of Texas Southwestern Medical Center in Dallas. Her laboratory has discovered rare pathogenic variants in several genes (<i>TERT</i>, <i>TERC</i>, <i>SFTPA2</i>, <i>PARN</i>, <i>RTEL1</i>) in patients with <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> pulmonary fibrosis. These discoveries have linked the telomere and surfactant pathways to adult-onset fibrotic interstitial lung diseases. She and her colleagues have shown that leukocyte telomere length is a biomarker that predicts clinical outcomes for patients, including survival, rate of progression, and response to immunosuppressive medications. Dr Garcia holds appointments in the Department of Medicine, the Institute for Genomic Medicine, and the Center for Precision Medicine and Genomics.</p><p>Janet Talbert earned her Master of Science (MS) in Biophysics and Genetics at the University of Colorado Medical Campus. She became a Diplomate of the American Board of Genetic Counselors (ABGC) in 2009. She is a member of the National Society of Genetic Counselors (NSGC) and the American Board of Genetic Counselors (ABGC). She worked in the Interstitial Lung Disease Program at National Jewish Health from 2003 to 2020 in roles that included oversight of a national <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> pulmonary fibrosis genetic study that lead to discovery of several SNPs associated with IPF/FPF, providing <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> services for the institution at large and to patients and families with FPF, genetic services manager (molecular laboratory report writing, provider-to-provider genetic services, and genetic test development) and a genetic advisor to the institution. She was the director of the Familial Pulmonary Fibrosis Genetic Counseling telephone line at National Jewish Health from 2008 to 2020. She serves on the Medical Advisory Board of the Pulmonary Fibrosis Foundation (PFF) and is part of an education outreach Ambassador Program for the PFF. From 2014 to 2015 she worked as faculty at the University of Colorado in the Hereditary Cancer clinic and from 2015 to 2020 at InformedDNA as a Senior Genetic Counselor performing genetic counseling via telehealth to patients nationwide with personal or family histories of cancer, inherited retinal disease, neurologic disorders, and FPF. As of 2021 she is an Associate Faculty member in Pediatrics, Division of Medical Genetics and Genomic Medicine, Vanderbilt University and Vanderbilt University Medical Center.</p></div><div id="pf.Author_History"><h3>Author History</h3><p>Christine Kim Garcia, MD, PhD (2021-present)<br />David Schwartz, MD; National Jewish Health (2005-2021)<br />Janet Talbert, MS, CGC (2010-present)<br />Anastasia Wise, PhD; National Jewish Health (2005-2010)</p></div><div id="pf.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>12 May 2022 (aa) Revision: edited information on <a href="/books/n/gene/dkc/">DC/TBD</a> in <a href="/books/NBK1230/table/pf.T.syndromes_in_which_pulmonary_fibros/?report=objectonly" target="object" rid-ob="figobpfTsyndromesinwhichpulmonaryfibros">Table 2</a></div></li><li class="half_rhythm"><div>11 February 2021 (sw) Comprehensive update posted live; scope changed to overview</div></li><li class="half_rhythm"><div>19 March 2015 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>19 October 2010 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>11 June 2007 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>21 January 2005 (me) Review posted live</div></li><li class="half_rhythm"><div>8 April 2004 (ds) Original submission</div></li></ul></div></div><div id="pf.References"><h2 id="_pf_References_">References</h2><div id="pf.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="pf.REF.alder.2011.e1001352">Alder
|
||
JK, Cogan
|
||
JD, Brown
|
||
AF, Anderson
|
||
CJ, Lawson
|
||
WE, Lansdorp
|
||
PM, Phillips
|
||
JA
|
||
3rd, Loyd
|
||
JE, Chen
|
||
JJ, Armanios
|
||
M. Ancestral mutation in telomerase causes defects in repeat addition processivity and manifests as familial pulmonary fibrosis.
|
||
PLoS Genet.
|
||
2011;7:e1001352.
|
||
[<a href="/pmc/articles/PMC3069110/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3069110</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21483807" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21483807</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.alder.2013.1481">Alder
|
||
JK, Parry
|
||
EM, Yegnasubramanian
|
||
S, Wagner
|
||
CL, Lieblich
|
||
LM, Auerbach
|
||
R, Auerbach
|
||
AD, Wheelan
|
||
SJ, Armanios
|
||
M. Telomere phenotypes in females with heterozygous mutations in the dyskeratosis congenita 1 (DKC1) gene.
|
||
Hum Mutat.
|
||
2013;34:1481-5.
|
||
[<a href="/pmc/articles/PMC3926107/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3926107</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23946118" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23946118</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.alder.2015.1361">Alder
|
||
JK, Stanley
|
||
SE, Wagner
|
||
CL, Hamilton
|
||
M, Hanumanthu
|
||
VS, Armanios
|
||
M. Exome sequencing identifies mutant TINF2 in a family with pulmonary fibrosis.
|
||
Chest.
|
||
2015;147:1361-8.
|
||
[<a href="/pmc/articles/PMC4420184/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4420184</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25539146" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25539146</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.armanios.2009.45">Armanios
|
||
M.
|
||
Syndromes of telomere shortening.
|
||
Annu Rev Genomics Hum Genet.
|
||
2009;10:45-61.
|
||
[<a href="/pmc/articles/PMC2818564/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2818564</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19405848" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19405848</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.armanios.2005.15960">Armanios
|
||
M, Chen
|
||
JL, Chang
|
||
YP, Brodsky
|
||
RA, Hawkins
|
||
A, Griffin
|
||
CA, Eshleman
|
||
JR, Cohen
|
||
AR, Chakravarti
|
||
A, Hamosh
|
||
A, Greider
|
||
CW. Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita.
|
||
Proc Natl Acad Sci U S A.
|
||
2005;102:15960-4.
|
||
[<a href="/pmc/articles/PMC1276104/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1276104</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16247010" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16247010</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.borie.2015.538">Borie
|
||
R, Kannengiesser
|
||
C, Hirschi
|
||
S, Le Pavec
|
||
J, Mal
|
||
H, Bergot
|
||
E, Jouneau
|
||
S, Naccache
|
||
JM, Revy
|
||
P, Boutboul
|
||
D, Peffault de la Tour
|
||
R, Wemeau-Stervinou
|
||
L, Philit
|
||
F, Cordier
|
||
JF, Thabut
|
||
G, Crestani
|
||
B, Cottin
|
||
V, et al.
|
||
Severe hematologic complications after lung transplantation in patients with telomerase complex mutations.
|
||
J Heart Lung Transplant.
|
||
2015;34:538-46.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/25612863" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25612863</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.borie.2017.160122">Borie
|
||
R, Kannengiesser
|
||
C, Sicre de Fontbrune
|
||
F, Gouya
|
||
L, Nathan
|
||
N, Crestani
|
||
B.
|
||
Management of suspected monogenic lung fibrosis in a specialised centre.
|
||
Eur Respir Rev.
|
||
2017;26:160122.
|
||
[<a href="/pmc/articles/PMC9489110/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9489110</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28446600" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28446600</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.borie.2016.1721">Borie
|
||
R, Tabeze
|
||
L, Thabut
|
||
G, Nunes
|
||
H, Cottin
|
||
V, Marchand-Adam
|
||
S, Prevot
|
||
G, Tazi
|
||
A, Cadranel
|
||
J, Mal
|
||
H, Wemeau-Stervinou
|
||
L, Bergeron Lafaurie
|
||
A, Israel-Biet
|
||
D, Picard
|
||
C, Reynaud Gaubert
|
||
M, Jouneau
|
||
S, Naccache
|
||
JM, Mankikian
|
||
J, Ménard
|
||
C, Cordier
|
||
JF, Valeyre
|
||
D, Reocreux
|
||
M, Grandchamp
|
||
B, Revy
|
||
P, Kannengiesser
|
||
C, Crestani
|
||
B. Prevalence and characteristics of TERT and TERC mutations in suspected genetic pulmonary fibrosis.
|
||
Eur Respir J.
|
||
2016;48:1721-31.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/27836952" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27836952</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.campo.2014.43">Campo
|
||
I, Zorzetto
|
||
M, Mariani
|
||
F, Kadija
|
||
Z, Morbini
|
||
P, Dore
|
||
R, Kaltenborn
|
||
E, Frixel
|
||
S, Zarbock
|
||
R, Liebisch
|
||
G, Hegermann
|
||
J, Wrede
|
||
C, Griese
|
||
M, Luisetti
|
||
M.
|
||
A large kindred of pulmonary fibrosis associated with a novel ABCA3 gene variant.
|
||
Respir Res.
|
||
2014;15:43.
|
||
[<a href="/pmc/articles/PMC4021316/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4021316</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24730976" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24730976</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.diaz_de_leon.2010.e10680">Diaz de Leon
|
||
A, Cronkhite
|
||
JT, Katzenstein
|
||
AL, Godwin
|
||
JD, Raghu
|
||
G, Glazer
|
||
CS, Rosenblatt
|
||
RL, Girod
|
||
CE, Garrity
|
||
ER, Xing
|
||
C, Garcia
|
||
CK. Telomere lengths, pulmonary fibrosis and telomerase (TERT) mutations.
|
||
PLoS ONE.
|
||
2010;5:e10680.
|
||
[<a href="/pmc/articles/PMC2873288/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2873288</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20502709" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20502709</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.dressen.2018.603">Dressen
|
||
A, Abbas
|
||
AR, Cabanski
|
||
C, Reeder
|
||
J, Ramalingam
|
||
TR, Neighbors
|
||
M, Bhangale
|
||
TR, Brauer
|
||
MJ, Hunkapiller
|
||
J, Reeder
|
||
J, Mukhyala
|
||
K, Cuenco
|
||
K, Tom
|
||
J, Cowgill
|
||
A, Vogel
|
||
J, Forrest
|
||
WF, Collard
|
||
HR, Wolters
|
||
PJ, Kropski
|
||
JA, Lancaster
|
||
LH, Blackwell
|
||
TS, Arron
|
||
JR, Yaspan
|
||
BL. Analysis of protein-altering variants in telomerase genes and their association with MUC5B common variant status in patients with idiopathic pulmonary fibrosis: a candidate gene sequencing study.
|
||
Lancet Respir Med.
|
||
2018;6:603-4.
|
||
[<a href="/pmc/articles/PMC6487850/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6487850</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29891356" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29891356</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.epaud.2014.638">Epaud
|
||
R, Delestrain
|
||
C, Louha
|
||
M, Simon
|
||
S, Fanen
|
||
P, Tazi
|
||
A. Combined pulmonary fibrosis and emphysema syndrome associated with ABCA3 mutations.
|
||
Eur Respir J.
|
||
2014;43:638-41.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/24136335" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24136335</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.flaherty.2019.1718">Flaherty
|
||
KR, Wells
|
||
AU, Cottin
|
||
V, Devaraj
|
||
A, Walsh
|
||
SLF, Inoue
|
||
Y, Richeldi
|
||
L, Kolb
|
||
M, Tetzlaff
|
||
K, Stowasser
|
||
S, Coeck
|
||
C, Clerisme-Beaty
|
||
E, Rosenstock
|
||
B, Quaresma
|
||
M, Haeufel
|
||
T, Goeldner
|
||
RG, Schlenker-Herceg
|
||
R, Brown
|
||
KK, et al.
|
||
Nintedanib in progressive fibrosing interstitial lung diseases.
|
||
N Engl J Med.
|
||
2019;381:1718-27.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/31566307" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31566307</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.george.2015.1549">George
|
||
G, Rosas
|
||
IO, Cui
|
||
Y, McKane
|
||
C, Hunninghake
|
||
GM, Camp
|
||
PC, Raby
|
||
BA, Goldberg
|
||
HJ, El-Chemaly
|
||
S. Short telomeres, telomeropathy, and subclinical extrapulmonary organ damage in patients with interstitial lung disease.
|
||
Chest.
|
||
2015;147:1549-57.
|
||
[<a href="/pmc/articles/PMC4451709/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4451709</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25393420" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25393420</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.gorgy.2015.1019">Gorgy
|
||
AI, Jonassaint
|
||
NL, Stanley
|
||
SE, Koteish
|
||
A, DeZern
|
||
AE, Walter
|
||
JE, Sopha
|
||
SC, Hamilton
|
||
JP, Hoover-Fong
|
||
J, Chen
|
||
AR, Anders
|
||
RA, Kamel
|
||
IR, Armanios
|
||
M. Hepatopulmonary syndrome is a frequent cause of dyspnea in the short telomere disorders.
|
||
Chest.
|
||
2015;148:1019-26.
|
||
[<a href="/pmc/articles/PMC4594621/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4594621</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26158642" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26158642</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.gutierrezrodrigues.2019.1594">Gutierrez-Rodrigues
|
||
F, Donaires
|
||
FS, Pinto
|
||
A, Vicente
|
||
A, Dillon
|
||
LW, Cle
|
||
DV, Santana
|
||
BA, Pirooznia
|
||
M, Ibanez
|
||
MDPF, Townsley
|
||
DM, Kajigaya
|
||
S, Hourigan
|
||
CS, Cooper
|
||
JN, Calado
|
||
RT, Young
|
||
NS. Pathogenic TERT promoter variants in telomere diseases.
|
||
Genet Med.
|
||
2019;21:1594-602.
|
||
[<a href="/pmc/articles/PMC6555700/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6555700</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30523342" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30523342</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.huang.2022.389">Huang
|
||
SJ, Amendola
|
||
LM, Sternen
|
||
DL. Variation among DNA banking consent forms: points for clinicians to bank on.
|
||
J Community Genet.
|
||
2022;13:389-97.
|
||
[<a href="/pmc/articles/PMC9314484/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9314484</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35834113" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35834113</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.j_nsson.2017.519">Jónsson
|
||
H, Sulem
|
||
P, Kehr
|
||
B, Kristmundsdottir
|
||
S, Zink
|
||
F, Hjartarson
|
||
E, Hardarson
|
||
MT, Hjorleifsson
|
||
KE, Eggertsson
|
||
HP, Gudjonsson
|
||
SA, Ward
|
||
LD, Arnadottir
|
||
GA, Helgason
|
||
EA, Helgason
|
||
H, Gylfason
|
||
A, Jonasdottir
|
||
A, Jonasdottir
|
||
A, Rafnar
|
||
T, Frigge
|
||
M, Stacey
|
||
SN, Th Magnusson
|
||
O, Thorsteinsdottir
|
||
U, Masson
|
||
G, Kong
|
||
A, Halldorsson
|
||
BV, Helgason
|
||
A, Gudbjartsson
|
||
DF, Stefansson
|
||
K. Parental influence on human germline de novo mutations in 1,548 trios from Iceland.
|
||
Nature.
|
||
2017;549:519-22.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/28959963" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28959963</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.juge.2017.1602314">Juge
|
||
PA, Borie
|
||
R, Kannengiesser
|
||
C, Gazal
|
||
S, Revy
|
||
P, Wemeau-Stervinou
|
||
L, Debray
|
||
MP, Ottaviani
|
||
S, Marchand-Adam
|
||
S, Nathan
|
||
N, Thabut
|
||
G, Richez
|
||
C, Nunes
|
||
H, Callebaut
|
||
I, Justet
|
||
A, Leulliot
|
||
N, Bonnefond
|
||
A, Salgado
|
||
D, Richette
|
||
P, Desvignes
|
||
JP, Lioté
|
||
H, Froguel
|
||
P, Allanore
|
||
Y, Sand
|
||
O, Dromer
|
||
C, Flipo
|
||
RM, Clément
|
||
A, Béroud
|
||
C, Sibilia
|
||
J, Coustet
|
||
B, Cottin
|
||
V, Boissier
|
||
MC, Wallaert
|
||
B, Schaeverbeke
|
||
T, Dastot le Moal
|
||
F, Frazier
|
||
A, Ménard
|
||
C, Soubrier
|
||
M, Saidenberg
|
||
N, Valeyre
|
||
D, Amselem
|
||
S, Boileau
|
||
C, Crestani
|
||
B, Dieudé
|
||
P, et al.
|
||
Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis.
|
||
Eur Respir J.
|
||
2017;49:1602314.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/28495692" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28495692</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.justet.2021.2003198">Justet
|
||
A, Klay
|
||
D, Porcher
|
||
R, Cottin
|
||
V, Ahmad
|
||
K, Molina Molina
|
||
M, Nunes
|
||
H, Reynaud-Gaubert
|
||
M, Naccache
|
||
JM, Manali
|
||
E, Froidure
|
||
A, Jouneau
|
||
S, Wemeau
|
||
L, Andrejak
|
||
C, Gondouin
|
||
A, Hirschi
|
||
S, Blanchard
|
||
E, Bondue
|
||
B, Bonniaud
|
||
P, Tromeur
|
||
C, Prévot
|
||
G, Marchand-Adam
|
||
S, Funke-Chambour
|
||
M, Gamez
|
||
AS, Ba
|
||
I, Papiris
|
||
S, Grutters
|
||
J, Crestani
|
||
B, Van Moorsel
|
||
C, Kannengiesser
|
||
C, Borie
|
||
R, et al.
|
||
Safety and efficacy of pirfenidone and nintedanib in patients with Idiopathic Pulmonary Fibrosis and carrying a telomere related gene mutation.
|
||
Eur Respir J.
|
||
2021;57:2003198.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/33214205" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33214205</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.king.2014.2083">King
|
||
TE
|
||
Jr, Bradford
|
||
WZ, Castro-Bernardini
|
||
S, Fagan
|
||
EA, Glaspole
|
||
I, Glassberg
|
||
MK, Gorina
|
||
E, Hopkins
|
||
PM, Kardatzke
|
||
D, Lancaster
|
||
L, Lederer
|
||
DJ, Nathan
|
||
SD, Pereira
|
||
CA, Sahn
|
||
SA, Sussman
|
||
R, Swigris
|
||
JJ, Noble
|
||
PW, et al.
|
||
A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis.
|
||
N Engl J Med.
|
||
2014;370:2083-92.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/24836312" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24836312</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.kropski.2014.e1">Kropski
|
||
JA, Mitchell
|
||
DB, Markin
|
||
C, Polosukhin
|
||
VV, Choi
|
||
L, Johnson
|
||
JE, Lawson
|
||
WE, Phillips
|
||
JA
|
||
3rd, Cogan
|
||
JD, Blackwell
|
||
TS, Loyd
|
||
JE. A novel dyskerin (DKC1) mutation is associated with familial interstitial pneumonia.
|
||
Chest.
|
||
2014;146:e1-7.
|
||
[<a href="/pmc/articles/PMC4077414/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4077414</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24504062" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24504062</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.kropski.2017.1423">Kropski
|
||
JA, Young
|
||
LR, Cogan
|
||
JD, Mitchell
|
||
DB, Lancaster
|
||
LH, Worrell
|
||
JA, Markin
|
||
C, Liu
|
||
N, Mason
|
||
WR, Fingerlin
|
||
TE, Schwartz
|
||
DA, Lawson
|
||
WE, Blackwell
|
||
TS, Phillips
|
||
JA
|
||
3rd, Loyd
|
||
JE. Genetic evaluation and testing of patients and families with idiopathic pulmonary fibrosis.
|
||
Am J Respir Crit Care Med.
|
||
2017;195:1423-8.
|
||
[<a href="/pmc/articles/PMC5470751/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5470751</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27786550" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27786550</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.lee.2012.1577">Lee
|
||
HY, Seo
|
||
JB, Steele
|
||
MP, Schwarz
|
||
MI, Brown
|
||
KK, Loyd
|
||
JE, Talbert
|
||
JL, Schwartz
|
||
DA, Lynch
|
||
DA. High-resolution CT scan findings in familial interstitial pneumonia do not conform to those of idiopathic interstitial pneumonia.
|
||
Chest.
|
||
2012;142:1577-83.
|
||
[<a href="/pmc/articles/PMC3515030/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3515030</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23364926" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23364926</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.maher.2020.147">Maher
|
||
TM, Corte
|
||
TJ, Fischer
|
||
A, Kreuter
|
||
M, Lederer
|
||
DJ, Molina-Molina
|
||
M, Axmann
|
||
J, Kirchgaessler
|
||
KU, Samara
|
||
K, Gilberg
|
||
F, Cottin
|
||
V. Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: a double-blind, randomised, placebo-controlled, phase 2 trial.
|
||
Lancet Respir Med.
|
||
2020;8:147-57.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/31578169" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31578169</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.maryoung.2017.982">Maryoung
|
||
L, Yue
|
||
Y, Young
|
||
A, Newton
|
||
CA, Barba
|
||
C, van Oers
|
||
NS, Wang
|
||
RC, Garcia
|
||
CK. Somatic mutations in telomerase promoter counterbalance germline loss-of-function mutations.
|
||
J Clin Invest.
|
||
2017;127:982-6.
|
||
[<a href="/pmc/articles/PMC5330735/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5330735</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28192371" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28192371</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.mechri.2010.1021">Mechri
|
||
M, Epaud
|
||
R, Emond
|
||
S, Coulomb
|
||
A, Jaubert
|
||
F, Tarrant
|
||
A, Feldmann
|
||
D, Flamein
|
||
F, Clement
|
||
A, de Blic
|
||
J, Taam
|
||
RA, Brunelle
|
||
F, le Pointe
|
||
HD. Surfactant protein C gene (SFTPC) mutation-associated lung disease: high-resolution computed tomography (HRCT) findings and its relation to histological analysis.
|
||
Pediatr Pulmonol.
|
||
2010;45:1021-9.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/20658481" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20658481</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.nathan.2016.1457">Nathan
|
||
N, Giraud
|
||
V, Picard
|
||
C, Nunes
|
||
H, Dastot-Le Moal
|
||
F, Copin
|
||
B, Galeron
|
||
L, De Ligniville
|
||
A, Kuziner
|
||
N, Reynaud-Gaubert
|
||
M, Valeyre
|
||
D, Couderc
|
||
LJ, Chinet
|
||
T, Borie
|
||
R, Crestani
|
||
B, Simansour
|
||
M, Nau
|
||
V, Tissier
|
||
S, Duquesnoy
|
||
P, Mansour-Hendili
|
||
L, Legendre
|
||
M, Kannengiesser
|
||
C, Coulomb-L'Hermine
|
||
A, Gouya
|
||
L, Amselem
|
||
S, Clement
|
||
A. Germline SFTPA1 mutation in familial idiopathic interstitial pneumonia and lung cancer.
|
||
Hum Mol Genet.
|
||
2016;25:1457-67.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/26792177" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26792177</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.newton.2016.1710">Newton
|
||
CA, Batra
|
||
K, Torrealba
|
||
J, Kozlitina
|
||
J, Glazer
|
||
CS, Aravena
|
||
C, Meyer
|
||
K, Raghu
|
||
G, Collard
|
||
HR, Garcia
|
||
CK. Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive.
|
||
Eur Respir J.
|
||
2016;48:1710-20.
|
||
[<a href="/pmc/articles/PMC5433348/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5433348</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27540018" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27540018</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.nunes.2017.1602022">Nunes
|
||
H, Jeny
|
||
F, Bouvry
|
||
D, Picard
|
||
C, Bernaudin
|
||
JF, Ménard
|
||
C, Brillet
|
||
PY, Kannengiesser
|
||
C, Valeyre
|
||
D, Kambouchner
|
||
M. Pleuroparenchymal fibroelastosis associated with telomerase reverse transcriptase mutations.
|
||
Eur Respir J.
|
||
2017;49:1602022.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/28495689" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28495689</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.nunes.2014.753">Nunes
|
||
H, Monnet
|
||
I, Kannengiesser
|
||
C, Uzunhan
|
||
Y, Valeyre
|
||
D, Kambouchner
|
||
M, Naccache
|
||
JM. Is telomeropathy the explanation for combined pulmonary fibrosis and emphysema syndrome? report of a family with TERT mutation.
|
||
Am J Respir Crit Care Med.
|
||
2014;189:753-4.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/24628319" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24628319</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.okamoto.2013.384">Okamoto
|
||
T, Miyazaki
|
||
Y, Tomita
|
||
M, Tamaoka
|
||
M, Inase
|
||
N.
|
||
A familial history of pulmonary fibrosis in patients with chronic hypersensitivity pneumonitis.
|
||
Respiration.
|
||
2013;85:384-90.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/22688445" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22688445</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.popescu.2019.362">Popescu
|
||
I, Mannem
|
||
H, Winters
|
||
SA, Hoji
|
||
A, Silveira
|
||
F, McNally
|
||
E, Pipeling
|
||
MR, Lendermon
|
||
EA, Morrell
|
||
MR, Pilewski
|
||
JM, Hanumanthu
|
||
VS, Zhang
|
||
Y, Gulati
|
||
S, Shah
|
||
PD, Iasella
|
||
CJ, Ensor
|
||
CR, Armanios
|
||
M, McDyer
|
||
JF. Impaired cytomegalovirus immunity in idiopathic pulmonary fibrosis lung transplant recipients with short telomeres.
|
||
Am J Respir Crit Care Med.
|
||
2019;199:362-76.
|
||
[<a href="/pmc/articles/PMC6363970/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6363970</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30088779" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30088779</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.rahbari.2016.126">Rahbari
|
||
R, Wuster
|
||
A, Lindsay
|
||
SJ, Hardwick
|
||
RJ, Alexandrov
|
||
LB, Turki
|
||
SA, Dominiczak
|
||
A, Morris
|
||
A, Porteous
|
||
D, Smith
|
||
B, Stratton
|
||
MR, Hurles
|
||
ME, et al.
|
||
Timing, rates and spectra of human germline mutation.
|
||
Nat Genet.
|
||
2016;48:126-33.
|
||
[<a href="/pmc/articles/PMC4731925/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4731925</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26656846" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26656846</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.reddy.2012.377">Reddy
|
||
TL, Tominaga
|
||
M, Hansell
|
||
DM, von der Thusen
|
||
J, Rassl
|
||
D, Parfrey
|
||
H, Guy
|
||
S, Twentyman
|
||
O, Rice
|
||
A, Maher
|
||
TM, Renzoni
|
||
EA, Wells
|
||
AU, Nicholson
|
||
AG. Pleuroparenchymal fibroelastosis: a spectrum of histopathological and imaging phenotypes.
|
||
Eur Respir J.
|
||
2012;40:377-85.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/22441748" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22441748</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.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></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.richeldi.2014.2071">Richeldi
|
||
L, du Bois
|
||
RM, Raghu
|
||
G, Azuma
|
||
A, Brown
|
||
KK, Costabel
|
||
U, Cottin
|
||
V, Flaherty
|
||
KR, Hansell
|
||
DM, Inoue
|
||
Y, Kim
|
||
DS, Kolb
|
||
M, Nicholson
|
||
AG, Noble
|
||
PW, Selman
|
||
M, Taniguchi
|
||
H, Brun
|
||
M, Le Maulf
|
||
F, Girard
|
||
M, Stowasser
|
||
S, Schlenker-Herceg
|
||
R, Disse
|
||
B, Collard
|
||
HR, et al.
|
||
Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis.
|
||
N Engl J Med.
|
||
2014;370:2071-82.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/24836310" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24836310</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.salisbury.2020.1230">Salisbury
|
||
ML, Hewlett
|
||
JC, Ding
|
||
G, Markin
|
||
CR, Douglas
|
||
K, Mason
|
||
W, Guttentag
|
||
A, Phillips
|
||
JA
|
||
3rd, Cogan
|
||
JD, Reiss
|
||
S, Mitchell
|
||
DB, Wu
|
||
P, Young
|
||
LR, Lancaster
|
||
LH, Loyd
|
||
JE, Humphries
|
||
SM, Lynch
|
||
DA, Kropski
|
||
JA, Blackwell
|
||
TS. Development and progression of radiologic abnormalities in individuals at risk for familial interstitial lung disease.
|
||
Am J Respir Crit Care Med.
|
||
2020;201:1230-9.
|
||
[<a href="/pmc/articles/PMC7233345/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7233345</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32011901" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32011901</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.silhan.2014.178">Silhan
|
||
LL, Shah
|
||
PD, Chambers
|
||
DC, Snyder
|
||
LD, Riise
|
||
GC, Wagner
|
||
CL, Hellström-Lindberg
|
||
E, Orens
|
||
JB, Mewton
|
||
JF, Danoff
|
||
SK, Arcasoy
|
||
MO, Armanios
|
||
M. Lung transplantation in telomerase mutation carriers with pulmonary fibrosis.
|
||
Eur Respir J.
|
||
2014;44:178-87.
|
||
[<a href="/pmc/articles/PMC4076528/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4076528</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24833766" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24833766</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.snetselaar.2015.1011">Snetselaar
|
||
R, van Moorsel
|
||
CH, Kazemier
|
||
KM, van der Vis
|
||
JJ, Zanen
|
||
P, van Oosterhout
|
||
MF, Grutters
|
||
JC. Telomere length in interstitial lung diseases.
|
||
Chest.
|
||
2015;148:1011-8.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/25973743" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25973743</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.stanley.2015.563">Stanley
|
||
SE, Chen
|
||
JJ, Podlevsky
|
||
JD, Alder
|
||
JK, Hansel
|
||
NN, Mathias
|
||
RA, Qi
|
||
X, Rafaels
|
||
NM, Wise
|
||
RA, Silverman
|
||
EK, Barnes
|
||
KC, Armanios
|
||
M. Telomerase mutations in smokers with severe emphysema.
|
||
J Clin Invest.
|
||
2015;125:563-70.
|
||
[<a href="/pmc/articles/PMC4319417/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4319417</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25562321" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25562321</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.stanley.2016.351ra107">Stanley
|
||
SE, Gable
|
||
DL, Wagner
|
||
CL, Carlile
|
||
TM, Hanumanthu
|
||
VS, Podlevsky
|
||
JD, Khalil
|
||
SE, DeZern
|
||
AE, Rojas-Duran
|
||
MF, Applegate
|
||
CD, Alder
|
||
JK, Parry
|
||
EM, Gilbert
|
||
WV, Armanios
|
||
M. Loss-of-function mutations in the RNA biogenesis factor NAF1 predispose to pulmonary fibrosis-emphysema.
|
||
Sci Transl Med.
|
||
2016;8:351ra107.
|
||
[<a href="/pmc/articles/PMC5351811/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5351811</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27510903" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27510903</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.tokman.2015.1318">Tokman
|
||
S, Singer
|
||
JP, Devine
|
||
MS, Westall
|
||
GP, Aubert
|
||
JD, Tamm
|
||
M, Snell
|
||
GI, Lee
|
||
JS, Goldberg
|
||
HJ, Kukreja
|
||
J, Golden
|
||
JA, Leard
|
||
LE, Garcia
|
||
CK, Hays
|
||
SR. Clinical outcomes of lung transplant recipients with telomerase mutations.
|
||
J Heart Lung Transplant.
|
||
2015;34:1318-24.
|
||
[<a href="/pmc/articles/PMC5382798/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5382798</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26169663" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26169663</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.van_moorsel.2015.1249">van Moorsel
|
||
CH, Ten Klooster
|
||
L, van Oosterhout
|
||
MF, de Jong
|
||
PA, Adams
|
||
H, Wouter van Es
|
||
H, Ruven
|
||
HJ, van der Vis
|
||
JJ, Grutters
|
||
JC. SFTPA2 mutations in familial and sporadic idiopathic interstitial pneumonia.
|
||
Am J Respir Crit Care Med.
|
||
2015;192:1249-52.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/26568241" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26568241</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.van_moorsel.2010.1419">van Moorsel
|
||
CH, van Oosterhout
|
||
MF, Barlo
|
||
NP, de Jong
|
||
PA, van der Vis
|
||
JJ, Ruven
|
||
HJ, van Es
|
||
HW, van den Bosch
|
||
JM, Grutters
|
||
JC. Surfactant protein C mutations are the basis of a significant portion of adult familial pulmonary fibrosis in a Dutch cohort.
|
||
Am J Respir Crit Care Med.
|
||
2010;182:1419-25.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/20656946" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20656946</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.wang.2009.52">Wang
|
||
Y, Kuan
|
||
PJ, Xing
|
||
C, Cronkhite
|
||
JT, Torres
|
||
F, Rosenblatt
|
||
RL, DiMaio
|
||
JM, Kinch
|
||
LN, Grishin
|
||
NV, Garcia
|
||
CK. Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung cancer.
|
||
Am J Hum Genet.
|
||
2009;84:52-9.
|
||
[<a href="/pmc/articles/PMC2668050/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2668050</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19100526" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19100526</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.yoon.2018.195">Yoon
|
||
JH, Nouraie
|
||
M, Chen
|
||
X, Zou
|
||
RH, Sellares
|
||
J, Veraldi
|
||
KL, Chiarchiaro
|
||
J, Lindell
|
||
K, Wilson
|
||
DO, Kaminski
|
||
N, Burns
|
||
T, Trejo Bittar
|
||
H, Yousem
|
||
S, Gibson
|
||
K, Kass
|
||
DJ. Characteristics of lung cancer among patients with idiopathic pulmonary fibrosis and interstitial lung disease - analysis of institutional and population data.
|
||
Respir Res.
|
||
2018;19:195.
|
||
[<a href="/pmc/articles/PMC6171146/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6171146</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30285867" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30285867</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="pf.REF.zhang.2019.797">Zhang
|
||
D, Zhou
|
||
Z, Abu-Hijleh
|
||
M, Batra
|
||
K, Xing
|
||
C, Garcia
|
||
CK. Homozygous rare PARN missense mutation in familial pulmonary fibrosis.
|
||
Am J Respir Crit Care Med.
|
||
2019;199:797-9.
|
||
[<a href="/pmc/articles/PMC6423103/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6423103</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30525901" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30525901</span></a>]</div></li></ul></div></div><div id="bk_toc_contnr"></div></div></div>
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK1230/?report=reader">PubReader</a></li><li><a href="/books/NBK1230/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK1230" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK1230" style="display:none" title="Cite this Page"><div class="bk_tt">Garcia CK, Talbert JL. Pulmonary Fibrosis Predisposition Overview. 2005 Jan 21 [Updated 2022 May 12]. 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Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></div></div></li><li><a href="/books/NBK1230/pdf/Bookshelf_NBK1230.pdf">PDF version of this page</a> (532K)</li><li><a href="#" class="toggle-glossary-link" title="Enable/disable links to the glossary">Disable Glossary Links</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>In this GeneReview</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="page-toc" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="#pf.Summary" ref="log$=inpage&link_id=inpage">Summary</a></li><li><a href="#pf.Clinical_Characteristics_of_Pulmonary" ref="log$=inpage&link_id=inpage"> Clinical Characteristics of Pulmonary Fibrosis</a></li><li><a href="#pf.Genetic_Causes_of_Pulmonary_Fibrosis" ref="log$=inpage&link_id=inpage"> Genetic Causes of Pulmonary Fibrosis</a></li><li><a href="#pf.Differential_Diagnosis_of_Pulmonary_F" ref="log$=inpage&link_id=inpage"> Differential Diagnosis of Pulmonary Fibrosis</a></li><li><a href="#pf.Evaluation_Strategies_to_Identify_the" ref="log$=inpage&link_id=inpage"> Evaluation Strategies to Identify the Genetic Cause of Pulmonary Fibrosis in a Proband</a></li><li><a href="#pf.Management_of_Pulmonary_Fibrosis" ref="log$=inpage&link_id=inpage"> Management of Pulmonary Fibrosis</a></li><li><a href="#pf.Genetic_Counseling" ref="log$=inpage&link_id=inpage"> Genetic Counseling</a></li><li><a href="#pf.Resources" ref="log$=inpage&link_id=inpage">Resources</a></li><li><a href="#pf.Chapter_Notes" ref="log$=inpage&link_id=inpage">Chapter Notes</a></li><li><a href="#pf.References" ref="log$=inpage&link_id=inpage">References</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Bulk Download</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="https://ftp.ncbi.nlm.nih.gov/pub/litarch/ca/84/" ref="pagearea=source-links&targetsite=external&targetcat=link&targettype=uri">Bulk download GeneReviews data from FTP</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>GeneReviews Links</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/n/gene/advanced/"><i>GeneReviews</i> Advanced Search</a></li><li><a href="/books/n/gene/glossary/"><i>GeneReviews</i> Glossary</a></li><li><a href="/books/n/gene/resource_mats/">Resource Materials</a> <span class="bk_hlight1">NEW FEATURE</span></li><li><a href="/books/n/gene/updates/">New in <i>GeneReviews</i></a></li><li><a href="/books/n/gene/authors/">Author List</a></li><li><a href="/books/n/gene/prospective_authors/">For Current/Prospective Authors</a></li><li><a href="/books/n/gene/GRpersonnel/"><i>GeneReviews</i> Personnel</a></li><li><a href="/books/n/gene/howto_linkin/">Download/Link to <i>GeneReviews</i></a></li><li><a href="/books/n/gene/contact_us/">Contact Us</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Tests in GTR by Gene</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="document-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li>
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