{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:15:17Z","timestamp":1787613317259,"version":"build-2736575974"},"reference-count":21,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,3,22]],"date-time":"2025-03-22T00:00:00Z","timestamp":1742601600000},"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":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Perrault syndrome is a heterogeneous phenotype that generally encompasses the findings of sensorineural hearing loss in both 46,XX and 46,XY individuals and varying degrees of abnormal ovarian function in 46,XX individuals. In this case report, we present two brothers with <jats:italic>LARS2<\/jats:italic>\u2010related Perrault syndrome who have undervirilization. In addition to bilateral profound sensorineural hearing loss, both brothers had bilateral undescended testes that required surgical intervention. In addition, the younger affected brother had hypospadias with chordee. Quad exome sequencing on both brothers was consistent with 46,XY and revealed the same biallelic pathogenic variants in <jats:italic>LARS2<\/jats:italic>, a gene known to be associated with Perrault syndrome. No other variants were reported on exome analysis. To date, undervirilization in 46,XY individuals who have Perrault syndrome has only rarely been reported, although the number of reported males with Perrault syndrome continues to be small. Pathogenic variants in <jats:italic>LARS2<\/jats:italic> have been found to lead to ovarian dysgenesis in 46,XX individuals and complete infertility due to failure to produce germ cells in <jats:italic>Caenorhabditis elegans<\/jats:italic> (<jats:styled-content style=\"fixed-case\">\n<jats:italic>C<\/jats:italic>\n<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">\n<jats:italic>elegans<\/jats:italic>\n<\/jats:styled-content>), indicating that <jats:italic>LARS2<\/jats:italic> is expressed in gonadal tissue and can impact gonadal development. Undervirilization in affected males is likely an underrecognized component of the <jats:italic>LARS2<\/jats:italic>\u2010related Perrault syndrome. In this article, we suggest that <jats:italic>LARS2<\/jats:italic> be included in the differential diagnosis of both 46,XX and 46,XY individuals with DSD conditions and should be considered in 46,XY individuals with hearing loss and evidence of undervirilization.<\/jats:p>","DOI":"10.1002\/ajmg.a.64064","type":"journal-article","created":{"date-parts":[[2025,3,22]],"date-time":"2025-03-22T15:00:09Z","timestamp":1742655609000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<i>LARS2<\/i>\u2010Related Perrault Syndrome in Siblings With 46,XY Differences of Sex Development"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3437-1507","authenticated-orcid":false,"given":"Aaron P.","family":"Adam","sequence":"first","affiliation":[{"name":"Department of Biology Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"O'Sullivan","sequence":"additional","affiliation":[{"name":"Seattle Children's Hospital  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Peterson","sequence":"additional","affiliation":[{"name":"Seattle Children's Hospital  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Yabumoto","sequence":"additional","affiliation":[{"name":"Seattle Children's Hospital  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Merguerian","sequence":"additional","affiliation":[{"name":"Seattle Children's Hospital  Seattle Washington USA"},{"name":"Department of Urology University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9817-5121","authenticated-orcid":false,"given":"Margaret P.","family":"Adam","sequence":"additional","affiliation":[{"name":"Seattle Children's Hospital  Seattle Washington USA"},{"name":"Department of Pediatrics University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,22]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.9522"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201007784\u20109"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12776"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439\u2010021\u201002319\u20107"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac064"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2021.10.002"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.01.010"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38552"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn115330\u201020230329\u201000140"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010021\u201001242\u20106"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102265.2008.03392.x"},{"key":"e_1_2_12_13_1","volume-title":"GeneReviews","author":"Newman W. 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