{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:16:28Z","timestamp":1790007388872,"version":"4.0.1"},"reference-count":11,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T00:00:00Z","timestamp":1685836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Restrictive dermopathy (RD) is a lethal condition caused by biallelic loss\u2010of\u2010function mutations in <jats:italic>ZMPSTE24<\/jats:italic>, whereas mutations preserving residual enzymatic activity of the ZMPSTE24 protein lead to the milder mandibuloacral dysplasia with type B lipodystrophy (MADB) phenotype. Remarkably, we identified a homozygous, presumably loss\u2010of\u2010function mutation in <jats:italic>ZMPSTE24<\/jats:italic> [c.28_29insA, p.(Leu10Tyrfs*37)] in two consanguineous Pakistani families segregating MADB. To clarify how lethal consequences are prevented in affected individuals, functional analysis was performed. Expression experiments supported utilization of two alternative translation initiation sites, preventing complete loss of protein function consistent with the relatively mild phenotypic outcome in affected patients. One of these alternative start codons is newly formed at the insertion site. Our findings indicate that the creation of new potential start codons through N\u2010terminal mutations in other disease\u2010associated genes should generally be taken into consideration in the variant interpretation process.<\/jats:p>","DOI":"10.1111\/cge.14381","type":"journal-article","created":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T22:18:22Z","timestamp":1686003502000},"page":"491-496","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Analysis of a non\u2010lethal biallelic frameshift mutation in <scp><i>ZMPSTE24<\/i><\/scp> reveals utilization of alternative translation initiation codons"],"prefix":"10.1111","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8218-7486","authenticated-orcid":false,"given":"Lukas","family":"Kaufmann","sequence":"first","affiliation":[{"name":"Diagnostic and Research Institute of Human Genetics Medical University of Graz  Graz 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and Research Institute of Human Genetics Medical University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Al Kaissi","sequence":"additional","affiliation":[{"name":"Pediatric Orthopedic Department Speising Hospital  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muzammil Ahmad","family":"Khan","sequence":"additional","affiliation":[{"name":"Gomal Centre of Biochemistry and Biotechnology Gomal University  Dera Ismail Khan Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Windpassinger","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Institute of Human Genetics Medical University of Graz  Graz Austria"},{"name":"Neurogenetics Laboratory, Department of Neurology Medical University of Graz  Graz 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