{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:39:41Z","timestamp":1765546781235,"version":"3.40.5"},"reference-count":11,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT104033AIA","WT093205 MA"],"award-info":[{"award-number":["WT104033AIA","WT093205 MA"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Congenital Anomalies"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The Ehlers\u2013Danlos syndrome (EDS) is a group of heritable connective tissue disorders. Common features of EDS include skin hyperextensibility, articular hypermobility, and tissue fragility. It is classified into 13 subtypes, caused by variations of more than 19 different genes. Among these two subtypes, EDS musculocontractural type 1 (EDSMC1\/mcEDS\u2010<jats:italic>CHST14<\/jats:italic>; MIM# 601776) is caused by biallelic mutations in the <jats:italic>CHST14<\/jats:italic> gene (MIM# 608429) on chromosome 15q14 and EDS musculocontractural type 2 (EDSMC2\/mcEDS\u2010<jats:italic>DSE<\/jats:italic>;MIM#615539) is caused by a mutation in <jats:italic>DSE<\/jats:italic> (MIM# 605942) on chromosome 6q22. In this study, clinical and molecular diagnoses have been performed for a consanguineous Pakistani (Pakhtun) family with five affected siblings, presenting mcEDS\u2010<jats:italic>DSE<\/jats:italic> phenotype. Whole\u2010exome sequencing analysis identified a novel homozygous <jats:italic>DSE<\/jats:italic> variant (NM_001080976.1; c.2813T&gt;A, p.Val938Asp) in the proband. Sanger sequencing in all available affected members and their obligate carriers confirmed autosomal recessive segregation of the diseased allele. To the best of our knowledge, this variant identified is novel and expands the <jats:italic>DSE<\/jats:italic> pathogenicity leading to EDS, musculocontractural type 2. The result obtained has the potential to help in early diagnosis, genetic counseling, and possible therapeutic inventions.<\/jats:p>","DOI":"10.1111\/cga.12436","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T09:23:49Z","timestamp":1624958629000},"page":"177-182","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A novel variant in the <scp><i>DSE<\/i><\/scp> gene leads to <scp>Ehlers\u2013Danlos<\/scp> musculocontractural type 2 in a Pakistani family"],"prefix":"10.1111","volume":"61","author":[{"given":"Ikram","family":"Ullah","sequence":"first","affiliation":[{"name":"Centre for Omic Sciences Islamia College Peshawar  Peshawar Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Aamir","sequence":"additional","affiliation":[{"name":"Centre for Omic Sciences Islamia College Peshawar  Peshawar Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9357-123X","authenticated-orcid":false,"given":"Muhammad","family":"Ilyas","sequence":"additional","affiliation":[{"name":"Centre for Omic Sciences Islamia College Peshawar  Peshawar Pakistan"},{"name":"Centre for Human Genetics Hazara University Mansehra  Mansehra Pakistan"},{"name":"Queen Square Institute of Neurology University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akmal","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Centre for Human Genetics Hazara University Mansehra  Mansehra Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Musharraf","family":"Jelani","sequence":"additional","affiliation":[{"name":"Centre for Omic Sciences Islamia College Peshawar  Peshawar Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wahid","family":"Ullah","sequence":"additional","affiliation":[{"name":"Centre for Omic Sciences Islamia College Peshawar  Peshawar Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Abbas","sequence":"additional","affiliation":[{"name":"Centre for Omic Sciences Islamia College Peshawar  Peshawar Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Ishfaq","sequence":"additional","affiliation":[{"name":"Centre for Omic Sciences Islamia College Peshawar  Peshawar Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fawad","family":"Ali","sequence":"additional","affiliation":[{"name":"Neurology Unit Saidu Group of Teaching Hospitals  Swat Pakistan"},{"name":"Neurology Luqman International Hospital  Saidu Sharif Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janice","family":"Yip","sequence":"additional","affiliation":[{"name":"Queen Square Institute of Neurology University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Efthymiou","sequence":"additional","affiliation":[{"name":"Queen Square Institute of Neurology University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Habib","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Centre for Omic Sciences Islamia College Peshawar  Peshawar Pakistan"},{"name":"Centre for Human Genetics Hazara University Mansehra  Mansehra Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[{"name":"Queen Square Institute of Neurology University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,7,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31552"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2019.103798"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2013-304822"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/skinbio.2012.3"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471221929.ch9"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980428)77:1<31::AID-AJMG8>3.0.CO;2-O"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22774"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1197"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt227"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11010043"}],"container-title":["Congenital Anomalies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cga.12436","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cga.12436","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cga.12436","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T20:46:05Z","timestamp":1693341965000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cga.12436"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,13]]},"references-count":11,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["10.1111\/cga.12436"],"URL":"https:\/\/doi.org\/10.1111\/cga.12436","archive":["Portico"],"relation":{},"ISSN":["0914-3505","1741-4520"],"issn-type":[{"type":"print","value":"0914-3505"},{"type":"electronic","value":"1741-4520"}],"subject":[],"published":{"date-parts":[[2021,7,13]]},"assertion":[{"value":"2021-02-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}