{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:12:21Z","timestamp":1792113141877,"version":"4.4.0"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T00:00:00Z","timestamp":1676592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004054","name":"King Abdulaziz University","doi-asserted-by":"publisher","award":["IFPIP-1835-141-1443"],"award-info":[{"award-number":["IFPIP-1835-141-1443"]}],"id":[{"id":"10.13039\/501100004054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>(1) Background: Dyggve-Melchior-Clausen Syndrome is a skeletal dysplasia caused by a defect in the DYM gene (OMIM number 607461). Pathogenic variants in the gene have been reported to cause Dyggve-Melchior-Clausen (DMC; OMIM 223800) dysplasia and Smith-McCort (SMC; OMIM 607326) dysplasia. (2) Methods: In the present study, large consanguineous families with five affected individuals with osteochondrodysplasia phenotypes were recruited. The family members were analyzed by polymerase chain reaction for homozygosity mapping using highly polymorphic microsatellite markers. Subsequent to linkage analysis, the coding exons and exon intron border of the DYM gene were amplified. The amplified products were then sent for Sanger sequencing. The structural effect of the pathogenic variant was analyzed by different bioinformatics tools. (3) Results: Homozygosity mapping revealed a 9 Mb homozygous region on chromosome 18q21.1 harboring DYM shared by all available affected individuals. Sanger sequencing of the coding exons and exon intron borders of the DYM gene revealed a novel homozygous nonsense variant [DYM (NM_017653.6):c.1205T&gt;A, p.(Leu402Ter)] in affected individuals. All the available unaffected individuals were either heterozygous or wild type for the identified variant. The identified mutation results in loss of protein stability and weekend interactions with other proteins making them pathogenic (4) Conclusions: This is the second nonsense mutation reported in a Pakistani population causing DMC. The study presented would be helpful in prenatal screening, genetic counseling, and carrier testing of other members in the Pakistani community.<\/jats:p>","DOI":"10.3390\/genes14020510","type":"journal-article","created":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T02:27:24Z","timestamp":1676600844000},"page":"510","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Novel Homozygous Nonsense Variant in the DYM Underlies Dyggve-Melchior-Clausen Syndrome in Large Consanguineous Family"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9331-3468","authenticated-orcid":false,"given":"Abu","family":"Bakar","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7792-1180","authenticated-orcid":false,"given":"Sulaiman","family":"Shams","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nousheen","family":"Bibi","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Shaheed Benazir Bhutto Women University, Peshawar 25120, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5715-3425","authenticated-orcid":false,"given":"Asmat","family":"Ullah","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark"},{"name":"Department of Biochemistry, Quaid-I-Azam University, Islamabad 45320, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wasim","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Quaid-I-Azam University, Islamabad 45320, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3421-0079","authenticated-orcid":false,"given":"Musharraf","family":"Jelani","sequence":"additional","affiliation":[{"name":"Rare Diseases Genetics and Genomics, Centre for Omic Sciences, Islamia College Peshawar, Peshawar 25120, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3458-1697","authenticated-orcid":false,"given":"Osama Yousef","family":"Muthaffar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angham Abdulrhman","family":"Abdulkareem","sequence":"additional","affiliation":[{"name":"Faculty of Science, Department of Biochemistry, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Turki S.","family":"Abujamel","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Absarul","family":"Haque","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21859, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Imran","family":"Naseer","sequence":"additional","affiliation":[{"name":"Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3239-496X","authenticated-orcid":false,"given":"Bushra","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s00247-002-0855-8","article-title":"Radiological diagnosis of the constitutional disorders of bone. 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