{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T23:19:25Z","timestamp":1773357565963,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T00:00:00Z","timestamp":1596758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["C201606055"],"award-info":[{"award-number":["C201606055"]}],"id":[{"id":"10.13039\/501100003787","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":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Distal arthrogryposis (DA) is a group of rare Mendelian conditions that demonstrate heterogeneity with respect to genetics and phenotypes. Ten types of DAs, which collectively involve six genes, have been reported. Among them, the <jats:italic>MYH3<\/jats:italic> gene causes several types of arthrogryposis conditions and therefore has a pivotal role in the skeletal and muscle development of the fetus. For this study, we recruited a five\u2010generation Chinese family with members presenting DA features and phenotypic variability. Further clinical study characterized it as CPSFS1A (Contractures, Pterygia, and Spondylocarpotarsal Fusion Syndrome 1A).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Genomic DNA was extracted from eight family members, including one fetus. Whole\u2010exome sequencing (WES) was then conducted on the proband's sample, followed by Sanger sequencing as validation for each of the participants. In silico analysis was performed. Western blotting (WB) detection and pathological staining were conducted on skeletal muscle tissue of the induced fetus after prenatal diagnosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel heterozygous pathogenic variant, namely NM_002470.3: c.3044_3047delinsTCAATTTGTT: p.E1015_D1016delinsVNLF in the <jats:italic>MYH3<\/jats:italic> gene, was identified and shown to be cosegregated with the condition in the subject family. This variant resulted in the replacement of amino\u2010acid residues E1015 and D1016 by a string of VNLFs. The pregnancy was selectively terminated because the fetus was genetically affected. However, the WB and pathological results did not indicate a significant change in the norm.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study expanded the variant spectrum of CPSFS1A, in addition to which it provided solid evidence for the appropriateness of genetic counseling and pregnancy management for the family. The results may also provide further insight into the molecular mechanism of <jats:italic>MYH3<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1440","type":"journal-article","created":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T23:07:00Z","timestamp":1596841620000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Identification of a novel pathogenic variant in the <i>MYH3<\/i> gene in a five\u2010generation family with CPSFS1A (Contractures, Pterygia, and Spondylocarpotarsal Fusion Syndrome 1A)"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9957-3372","authenticated-orcid":false,"given":"Jing","family":"Zhang","sequence":"first","affiliation":[{"name":"Center of Prenatal Diagnosis Shijiazhuang Obstetrics and Gynecology Hospital Shijiazhuang 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