{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T06:09:59Z","timestamp":1788934199896,"version":"build-2803163510"},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T00:00:00Z","timestamp":1707782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100015326","name":"Common Fund","doi-asserted-by":"publisher","award":["1U01HG010230"],"award-info":[{"award-number":["1U01HG010230"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Phenotypic features of a hereditary connective tissue disorder, including craniofacial characteristics, hyperextensible skin, joint laxity, kyphoscoliosis, arachnodactyly, inguinal hernia, and diverticulosis associated with biallelic pathogenic variants in <jats:italic>EFEMP1<\/jats:italic> have been previously described in four patients. Genome sequencing on a proband and her mother with comparable phenotypic features revealed that both patients were heterozygous for a stop\u2010gain variant c.1084C&gt;T (p.Arg362*). Complementary RNA\u2010seq on fibroblasts revealed significantly reduced levels of mutant <jats:italic>EFEMP1<\/jats:italic> transcript. Considering the absence of other molecular explanations, we extrapolated that <jats:italic>EFEMP1<\/jats:italic> could be the cause of the patient's phenotypes. Furthermore, nonsense\u2010mediated decay was demonstrated for the mutant allele as the principal mechanism for decreased levels of <jats:italic>EFEMP1<\/jats:italic> mRNA. We provide strong clinical and genetic evidence for the haploinsufficiency of <jats:italic>EFEMP1<\/jats:italic> due to nonsense\u2010medicated decay to cause severe kyphoscoliosis, generalized hypermobility of joints, high and narrow arched palate, and potentially severe diverticulosis. To the best of our knowledge, this is the first report of an autosomal dominant <jats:italic>EFEMP1\u2010<\/jats:italic>associated hereditary connective tissue disorder and therefore expands the phenotypic spectrum of <jats:italic>EFEMP1<\/jats:italic> related disorders.<\/jats:p>","DOI":"10.1002\/ajmg.a.63556","type":"journal-article","created":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T09:23:43Z","timestamp":1707816223000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp><i>EFEMP1<\/i><\/scp> haploinsufficiency causes a Marfan\u2010like hereditary connective tissue disorder"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5484-5186","authenticated-orcid":false,"given":"Irman","family":"Forghani","sequence":"first","affiliation":[{"name":"Department of Human Genetics University of Miami Miller School of Medicine  Miami Florida 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