{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T11:16:07Z","timestamp":1769253367987,"version":"3.49.0"},"reference-count":22,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T00:00:00Z","timestamp":1703203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006733","name":"Indiana University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006733","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":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>MBTPS1<\/jats:italic> (NM_003791.4) encodes Site\u20101 protease, a serine protease that functions sequentially with Site\u20102 protease regulating cholesterol homeostasis and endoplasmic reticulum stress response. <jats:italic>MBTPS1<\/jats:italic> pathogenic variants are associated with spondyloepiphyseal dysplasia, Kondo\u2010Fu type (MIM:618392; cataract, alopecia, oral mucosal disorder, and psoriasis\u2010like syndrome, and Silver\u2013Russell\u2010like syndrome). In this report, we describe a 14\u2010year\u2010old female with a complex medical history including white matter volume loss, early\u2010onset cataracts, retrognathia, laryngomalacia, inguinal hernia, joint hypermobility, feeding dysfunction, and speech delay. Additionally, features of ectodermal dysplasia that she has include decreased sweating, heat intolerance, dysplastic nails, chronically dry skin, and abnormal hair growth issues. Exome sequencing analysis identified compound heterozygous variants in the <jats:italic>MBTPS1<\/jats:italic> gene: c.2255G\u2009&gt;\u2009T p.(Gly752Val) predicted to affect important function of the protein, which was inherited from the mother, and a splice site variant c.2831\u2009+\u20095G\u2009&gt;\u2009T, which was inherited from the father. The RNA\u2010seq analysis of the splice variant showed skipping of exon 21, predicted to result in frameshifting p.(Ser901fs28*) leading to non\u2010sense mediated decay. To our knowledge, only eight studies have been published that described the <jats:italic>MBPTS1\u2010<\/jats:italic>related disorders. Interestingly, we observed the features of ectodermal dysplasia in our patient that further expands the phenotypic spectrum of <jats:italic>MBTPS1<\/jats:italic> gene\u2010related disorders.<\/jats:p>","DOI":"10.1002\/ajmg.a.63499","type":"journal-article","created":{"date-parts":[[2023,12,23]],"date-time":"2023-12-23T01:53:13Z","timestamp":1703296393000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A case of <scp><i>MBTPS1<\/i><\/scp>\u2010related disorder due to compound heterozygous variants in <scp><i>MBTPS1<\/i><\/scp> gene: Genotype\u2013phenotype expansion and the emergence of a novel syndrome"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0792-5773","authenticated-orcid":false,"given":"Khurram","family":"Liaqat","sequence":"first","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Undiagnosed Rare Disease Clinic (URDC), Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kayla","family":"Treat","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Undiagnosed Rare Disease Clinic (URDC), Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Mantcheva","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Undiagnosed Rare Disease Clinic (URDC), Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdul","family":"Nasir","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Second Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8312-8995","authenticated-orcid":false,"given":"David D.","family":"Weaver","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin","family":"Conboy","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Undiagnosed Rare Disease Clinic (URDC), Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Vetrini","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  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