{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T16:01:09Z","timestamp":1790524869780,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,12,11]],"date-time":"2018-12-11T00:00:00Z","timestamp":1544486400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:p>Biallelic variants in the <jats:italic>AEBP1<\/jats:italic> gene cause a novel autosomal\u2010recessive connective tissue disorder (CTD) reminiscent of Ehlers\u2010Danlos Syndrome (EDS). The four previously reported individuals show considerable clinical variability. Unbiased high\u2010throughput sequencing enables the rapid identification of additional cases for such rare entities. We identified the homozygous nonsense variant c.917dup, p.Tyr306* in <jats:italic>AEBP1<\/jats:italic> using clinical exome sequencing in a female individual with previously unsolved CTD. Segregation testing confirmed homozygosity in the clinically affected brother and heterozygous carrier status in the healthy mother. Chromosomal microarray showed that the variant lies in a run of homozygosity, suggesting a common origin of this genomic segment. RT\u2010PCR analysis in the mother revealed a monoallelic expression of the normal transcript supporting a nonsense\u2010mediated mRNA decay and functional nullizygosity as disease mechanism. We describe two individuals from a fourth family with <jats:italic>AEBP1<\/jats:italic>\u2010associated CTD. Our results further verify that autosomal\u2010recessive inherited LOF variants in the <jats:italic>AEBP1<\/jats:italic> gene cause clinical features of different EDS subtypes, but also of the marfanoid spectrum. As identification of further individuals is necessary to inform the clinical characterization, we stress the added value of exome sequencing for such rare diseases.<\/jats:p>","DOI":"10.1002\/ajmg.a.60679","type":"journal-article","created":{"date-parts":[[2018,12,12]],"date-time":"2018-12-12T07:28:40Z","timestamp":1544599720000},"page":"50-56","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["A biallelic truncating <i>AEBP1<\/i> variant causes connective tissue disorder in two siblings"],"prefix":"10.1002","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4651-7067","authenticated-orcid":false,"given":"Moritz","family":"Hebebrand","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg (FAU)  Erlangen 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