{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:15:33Z","timestamp":1792048533019,"version":"4.4.0"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,4,1]],"date-time":"2016-04-01T00:00:00Z","timestamp":1459468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2017,2]]},"abstract":"Perrault syndrome is a rare autosomal recessive disorder characterized by sensorineural hearing loss (SNHL<\/jats:styled-content>) in both sexes and primary ovarian insufficiency in 46, XX<\/jats:styled-content> karyotype females. Biallelic variants in five genes are reported to be causative: HSD17B4<\/jats:styled-content><\/jats:italic>, HARS2<\/jats:styled-content><\/jats:italic>, LARS2<\/jats:styled-content><\/jats:italic>, CLPP<\/jats:styled-content><\/jats:italic> and C10orf2<\/jats:italic>. Here we present eight families affected by Perrault syndrome. In five families we identified novel or previously reported variants in HSD17B4<\/jats:styled-content><\/jats:italic>, LARS2<\/jats:styled-content><\/jats:italic>, CLPP<\/jats:styled-content><\/jats:italic> and C10orf2<\/jats:styled-content><\/jats:italic>. The proband from each family was whole exome sequenced and variants confirmed by Sanger sequencing. A female was compound heterozygous for a known, p.(Gly16Ser<\/jats:styled-content>) and novel, p.(Val82Phe<\/jats:styled-content>) variant in D\u2010bifunctional protein (HSD17B4<\/jats:styled-content><\/jats:italic>). A family was homozygous for mitochondrial leucyl aminocyl tRNA synthetase (mtLeuRS<\/jats:styled-content>) (LARS2<\/jats:styled-content><\/jats:italic>) p.(Thr522Asn<\/jats:styled-content>), previously associated with Perrault syndrome. A further family was compound heterozygous for mtLeuRS<\/jats:styled-content>, p.(Thr522Asn<\/jats:styled-content>) and a novel variant, p.(Met117Ile<\/jats:styled-content>). Affected individuals with LARS2<\/jats:styled-content><\/jats:italic> variants had low frequency SNHL<\/jats:styled-content>, a feature previously described in Perrault syndrome. A female with significant neurological disability was compound heterozygous for p.(Arg323Gln<\/jats:styled-content>) and p.(Asn399Ser<\/jats:styled-content>) variants in Twinkle (C10orf2<\/jats:italic>). A male was homozygous for a novel variant in CLPP<\/jats:styled-content>, p.(Cys144Arg<\/jats:styled-content>). In three families there were no putative pathogenic variants in these genes confirming additional disease\u2010causing genes remain unidentified. We have expanded the spectrum of disease\u2010causing variants associated with Perrault syndrome.<\/jats:p>","DOI":"10.1111\/cge.12776","type":"journal-article","created":{"date-parts":[[2016,3,12]],"date-time":"2016-03-12T20:14:12Z","timestamp":1457813652000},"page":"302-312","source":"Crossref","is-referenced-by-count":91,"title":["Expanding the genotypic spectrum of Perrault syndrome"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8694-7710","authenticated-orcid":false,"given":"L.A.M.","family":"Demain","sequence":"first","affiliation":[{"name":"Manchester Centre for Genomic Medicine, Institute of Human Development University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.E.","family":"Urquhart","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine, Institute of Human Development University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"O'Sullivan","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine, Institute of Human Development University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.G.","family":"Williams","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine, Institute of Human Development University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.S.","family":"Bhaskar","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine, Institute of Human Development University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.M.","family":"Jenkinson","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine, Institute of Human Development University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.M.","family":"Lourenco","sequence":"additional","affiliation":[{"name":"Clinics Hospital of Ribeirao Preto University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Heiberg","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Oslo University Hospital Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.H.","family":"Pearce","sequence":"additional","affiliation":[{"name":"Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; and Endocrine Department Newcastle upon Tyne Hospitals Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.A.","family":"Shalev","sequence":"additional","affiliation":[{"name":"The Institute for Genetics Ha'Emek Medical Centre Afula Israel"},{"name":"Rapapport faculty of Medicine Technion Haifa Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.W.","family":"Yue","sequence":"additional","affiliation":[{"name":"Structural Genomics Consortium, Nuffield Department of Clinical Medicine University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Mackinnon","sequence":"additional","affiliation":[{"name":"Structural Genomics Consortium, Nuffield Department of Clinical Medicine University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.J.","family":"Munro","sequence":"additional","affiliation":[{"name":"School of Psychological Sciences University of Manchester Manchester UK"},{"name":"Central Manchester University Hospitals NHS Foundation Trust Manchester Academic Health Science Centre Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Newbury\u2010Ecob","sequence":"additional","affiliation":[{"name":"Clinical Genetics, St Michaels Hospital, Bristol Genetics Laboratory Pathology Sciences Southmead Hospital Bristol Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Becker","sequence":"additional","affiliation":[{"name":"Medical Genetics Center Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.J.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The Catholic University of Korea Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.T.","family":"O' Keefe","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.G.","family":"Newman","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine, Institute of Human Development University of Manchester Manchester UK"},{"name":"Central Manchester University Hospitals NHS Foundation Trust Manchester Academic Health Science Centre Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,4]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"Online Mendelian Inheritance in Man OMIM\u00ae. 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