{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:07:01Z","timestamp":1758845221513,"version":"3.44.0"},"reference-count":31,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Developmental dysplasia of the hip (DDH) is a prevalent congenital musculoskeletal disorder characterized by structural abnormalities of the hip joint. While its etiology involves genetic and environmental factors, specific genetic mechanisms remain poorly understood. Mutations in the <jats:italic>COMP<\/jats:italic> gene (<jats:italic>COMP<\/jats:italic>; OMIM: 600310), classically associated with skeletal dysplasias such as pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED), are rarely linked to isolated DDH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A 29\u2010year\u2010old male proband with familial DDH underwent clinical evaluation and radiographic imaging. Whole\u2010exome sequencing (WES) was performed on the proband and his parents, followed by Sanger sequencing to validate variants in affected family members. Pathogenicity was assessed using ACMG guidelines, incorporating population frequency, conservation scores (e.g., REVEL), and clinical correlation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>WES identified a heterozygous missense variant (<jats:italic>COMP<\/jats:italic> c.1133A&gt;C, p.D378A) in exon 10, co\u2010segregating with the DDH phenotype across three generations. Radiographic and clinical findings excluded PSACH and MED. Functional predictions (REVEL score: 0.84) and absence in population databases supported its classification as \u201clikely pathogenic.\u201d Additional susceptibility genes (e.g., <jats:italic>GDF5,<\/jats:italic> OMIM: 601146; <jats:italic>TBX4<\/jats:italic>, OMIM: 601719) were detected but did not explain the familial pattern.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The heterozygous <jats:italic>COMP<\/jats:italic> c.1133A&gt;C variant may be a highly penetrant pathogenic contributor to familial DDH in this pedigree, suggesting autosomal dominant inheritance. This finding suggests that <jats:italic>COMP<\/jats:italic> mutations might extend beyond classical skeletal dysplasias to significantly increase DDH risk, likely interacting with other genetic or environmental factors in line with the multifactorial etiology of DDH.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.70135","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T12:48:50Z","timestamp":1758631730000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Analysis of Familial Developmental Dysplasia of the Hip Associated With a Heterozygous Variant in the <i>COMP<\/i> Gene: A Case Report"],"prefix":"10.1002","volume":"13","author":[{"given":"Yan","family":"Miao","sequence":"first","affiliation":[{"name":"Women and Children's Hospital, Qingdao University  Qingdao Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0042-6995","authenticated-orcid":false,"given":"Jiashan","family":"Li","sequence":"additional","affiliation":[{"name":"Women and Children's Hospital, Qingdao University  Qingdao Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9173-826X","authenticated-orcid":false,"given":"Siying","family":"Liang","sequence":"additional","affiliation":[{"name":"Women and Children's Hospital, Qingdao University  Qingdao Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1017-9293","authenticated-orcid":false,"given":"Shuo","family":"Li","sequence":"additional","affiliation":[{"name":"Women and Children's Hospital, Qingdao University  Qingdao Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12755"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.30"},{"volume-title":"GeneReviews","year":"1993","author":"Briggs M. 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