{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:02:23Z","timestamp":1753869743005,"version":"3.41.2"},"reference-count":97,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,15]],"date-time":"2020-01-15T00:00:00Z","timestamp":1579046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004883","name":"Shahrekord University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004883","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Whole\u2010exome sequencing (WES) has emerged as a successful diagnostic tool in molecular genetics laboratories worldwide. In this study, we aimed to find the potential genetic cause of skeletal disease, a heterogeneous disease, revealing the obvious short stature phenotype. In an Iranian family, we used solo\u2010WES in a suspected patient to decipher the potential genetic cause(s).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A comprehensive clinical and genotyping examination was applied to suspect the disease of the patient. The solo clinical WES was exploited, and the derived data were filtered according to the standard pipelines. In order to validate the WES finding, the region harboring the candidate variant in the <jats:italic>CTSK<\/jats:italic> gene was amplified from genomic DNA and sequenced directly by Sanger sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sequence analysis revealed a rare novel nonsense variant, p.(Trp320*); c.905G&gt;A, in the <jats:italic>CTSK<\/jats:italic> gene (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"DDBJ\/EMBL\/GenBank\" xlink:href=\"NM_000396.3\">NM_000396.3<\/jats:ext-link>). In silico analysis shed light on the contribution of the variant to the pathogenicity of pycnodysostosis. This variant was confirmed by Sanger sequencing and further clinical examinations of the patient confirmed the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The present study shows a rare variant of the <jats:italic>CTSK<\/jats:italic> gene, which inherited as autosomal recessive, in an Iranian male patient with pycnodysostosis. Taken together, the novel nonsense <jats:italic>CTSK<\/jats:italic> variant meets the criteria of being likely pathogenic according to the American College of Medical Genetics and Genomics\u2010the Association for Molecular Pathology (ACMG\u2010AMP) variant interpretation guidelines.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1118","type":"journal-article","created":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T06:14:36Z","timestamp":1579155276000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Whole\u2010exome sequencing identified a novel variant in an Iranian patient affected by pycnodysostosis"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9926-3975","authenticated-orcid":false,"given":"Ehsan","family":"Razmara","sequence":"first","affiliation":[{"name":"Australian Regenerative Medicine Institute Monash University Clayton VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Homeyra","family":"Azimi","sequence":"additional","affiliation":[{"name":"Dr. Azimi Genetic Counseling Center Arak Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1495-0870","authenticated-orcid":false,"given":"Amirreza","family":"Bitaraf","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics Faculty of Biological Sciences Tarbiat Modares University Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Ali","family":"Daneshmand","sequence":"additional","affiliation":[{"name":"Daneshmand Pathology Laboratory Arak Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Galehdari","sequence":"additional","affiliation":[{"name":"Department of Biology Faculty of Sciences North Tehran Branch Islamic Azad University Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryam","family":"Dokhanchi","sequence":"additional","affiliation":[{"name":"Department of Biology, Science and Research Branch Islamic Azad University Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elika","family":"Esmaeilzadeh\u2010Gharehdaghi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Faculty of Medical Sciences Tarbiat Modares University Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5508-7903","authenticated-orcid":false,"given":"Masoud","family":"Garshasbi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Faculty of Medical Sciences Tarbiat Modares University Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,1,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/78107"},{"issue":"10","key":"e_1_2_10_3_1","first-page":"4630","article-title":"Analysis of the GNAS1 gene in Albright's hereditary osteodystrophy","volume":"86","author":"Ahrens W.","year":"2001","journal-title":"The Journal of Clinical Endocrinology & Metabolism"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22175"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/15513815.2013.807322"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1150110"},{"volume-title":"Kniest Displazi. 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