{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T07:49:25Z","timestamp":1753861765554,"version":"3.41.2"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:00:00Z","timestamp":1704844800000},"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":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>MPZL2<\/jats:italic>\u2010related hearing loss is a rare form of autosomal recessive hearing loss characterized by progressive, mild sloping to severe sensorineural hearing loss. Thirty\u2010five previously reported patients had biallelic truncating variants in <jats:italic>MPZL2<\/jats:italic>, with the exception of one patient with a missense variant of uncertain significance and a truncating variant. Here, we describe the clinical characteristics and genotypes of five patients from four families with confirmed <jats:italic>MPZL2<\/jats:italic>\u2010related hearing loss. A rare missense likely pathogenic variant [NM_005797.4(<jats:italic>MPZL2<\/jats:italic>):c.280C&gt;T,p.(Arg94Trp)] located in exon 3 was confirmed to be <jats:italic>in trans<\/jats:italic> with a recurrent pathogenic truncating variant that segregated with hearing loss in three of the patients from two unrelated families. This is the first recurrent likely pathogenic missense variant identified in <jats:italic>MPZL2<\/jats:italic>. Apparently milder or later\u2010onset hearing loss associated with rare missense variants in <jats:italic>MPZL2<\/jats:italic> indicates that some missense variants in this gene may cause a milder phenotype than that resulting from homozygous or compound heterozygous truncating variants. This study, along with the identification of truncating loss of function and missense <jats:italic>MPZL2<\/jats:italic> variants in several diverse populations, suggests that <jats:italic>MPZL2<\/jats:italic>\u2010related hearing loss may be more common than previously appreciated and demonstrates the need for <jats:italic>MPZL2<\/jats:italic> inclusion in hearing loss testing panels.<\/jats:p>","DOI":"10.1002\/ajmg.a.63530","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T11:55:37Z","timestamp":1704887737000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Recurrent missense variant identified in two unrelated families with <scp><i>MPZL2<\/i><\/scp>\u2010related hearing loss, expanding the variant spectrum associated with <scp>DFNB111<\/scp>"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3370-8260","authenticated-orcid":false,"given":"Emma","family":"Lo","sequence":"first","affiliation":[{"name":"Roberts Individualized Medical Genetics Center (RIMGC) Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin","family":"Blair","sequence":"additional","affiliation":[{"name":"Roberts Individualized Medical Genetics Center (RIMGC) Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuko","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Roberts Individualized Medical Genetics Center (RIMGC) Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Division of Otolaryngology, Department of Surgical Specialties National Center for Children's Health and Development  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Alejandra","family":"Diaz\u2010Miranda","sequence":"additional","affiliation":[{"name":"Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Bedoukian","sequence":"additional","affiliation":[{"name":"Roberts Individualized Medical Genetics Center (RIMGC) Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Gray","sequence":"additional","affiliation":[{"name":"Roberts Individualized Medical Genetics Center (RIMGC) Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Roberts Individualized Medical Genetics Center (RIMGC) Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kavita","family":"Dedhia","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Otorhinolaryngology \u2010 Head and Neck Surgery The Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa M.","family":"Elden","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Otorhinolaryngology \u2010 Head and Neck Surgery The Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A.","family":"Germiller","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Otorhinolaryngology \u2010 Head and Neck Surgery The Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Kazahaya","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Otorhinolaryngology \u2010 Head and Neck Surgery The Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven E.","family":"Sobol","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Otorhinolaryngology \u2010 Head and Neck Surgery The Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minjie","family":"Luo","sequence":"additional","affiliation":[{"name":"Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Pathology and Laboratory Medicine Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian D.","family":"Krantz","sequence":"additional","affiliation":[{"name":"Roberts Individualized Medical Genetics Center (RIMGC) Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Pediatrics Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiffiney R.","family":"Hartman","sequence":"additional","affiliation":[{"name":"Roberts Individualized Medical Genetics Center (RIMGC) Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Translational Medicine and Human Genetics Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,1,10]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_10_2_1","DOI":"10.1016\/j.ijporl.2020.110481"},{"doi-asserted-by":"publisher","key":"e_1_2_10_3_1","DOI":"10.1007\/s00439-018-1901-4"},{"doi-asserted-by":"publisher","key":"e_1_2_10_4_1","DOI":"10.1002\/lary.24332"},{"doi-asserted-by":"publisher","key":"e_1_2_10_5_1","DOI":"10.1186\/s12881-018-0541-9"},{"doi-asserted-by":"publisher","key":"e_1_2_10_6_1","DOI":"10.1016\/j.gim.2021.12.007"},{"doi-asserted-by":"publisher","key":"e_1_2_10_7_1","DOI":"10.1016\/j.neuroscience.2011.04.061"},{"doi-asserted-by":"publisher","key":"e_1_2_10_8_1","DOI":"10.1093\/nar\/gkh340"},{"doi-asserted-by":"publisher","key":"e_1_2_10_9_1","DOI":"10.1038\/gim.2018.48"},{"doi-asserted-by":"publisher","key":"e_1_2_10_10_1","DOI":"10.3389\/fgene.2021.707845"},{"doi-asserted-by":"publisher","key":"e_1_2_10_11_1","DOI":"10.1016\/j.ajhg.2016.08.016"},{"doi-asserted-by":"publisher","key":"e_1_2_10_12_1","DOI":"10.1038\/s41586-021-03819-2"},{"doi-asserted-by":"publisher","key":"e_1_2_10_13_1","DOI":"10.1001\/archoto.2009.202"},{"doi-asserted-by":"publisher","key":"e_1_2_10_14_1","DOI":"10.1038\/s41436-020-0774-9"},{"doi-asserted-by":"publisher","key":"e_1_2_10_15_1","DOI":"10.1093\/nar\/gkaa937"},{"doi-asserted-by":"publisher","key":"e_1_2_10_16_1","DOI":"10.1016\/j.ijporl.2023.111635"},{"doi-asserted-by":"publisher","key":"e_1_2_10_17_1","DOI":"10.1001\/jama.2020.17647"},{"doi-asserted-by":"publisher","key":"e_1_2_10_18_1","DOI":"10.1016\/j.jmoldx.2021.07.007"},{"doi-asserted-by":"publisher","key":"e_1_2_10_19_1","DOI":"10.1093\/nar\/gkac240"},{"doi-asserted-by":"publisher","key":"e_1_2_10_20_1","DOI":"10.3390\/jpm12111843"},{"doi-asserted-by":"publisher","key":"e_1_2_10_21_1","DOI":"10.1158\/0008-5472.CAN-15-0884"},{"doi-asserted-by":"publisher","key":"e_1_2_10_22_1","DOI":"10.1002\/humu.23630"},{"doi-asserted-by":"publisher","key":"e_1_2_10_23_1","DOI":"10.1002\/lary.30507"},{"doi-asserted-by":"publisher","key":"e_1_2_10_24_1","DOI":"10.1002\/humu.23042"},{"doi-asserted-by":"publisher","key":"e_1_2_10_25_1","DOI":"10.1038\/gim.2015.30"},{"volume-title":"RStudio: Integrated development for R","year":"2020","author":"RStudio Team","key":"e_1_2_10_26_1"},{"doi-asserted-by":"publisher","key":"e_1_2_10_27_1","DOI":"10.1038\/s41436-019-0535-9"},{"doi-asserted-by":"publisher","key":"e_1_2_10_28_1","DOI":"10.1002\/lary.29680"},{"doi-asserted-by":"publisher","key":"e_1_2_10_29_1","DOI":"10.1002\/ajmg.a.30726"},{"doi-asserted-by":"publisher","key":"e_1_2_10_30_1","DOI":"10.1016\/j.brainres.2016.06.031"},{"doi-asserted-by":"publisher","key":"e_1_2_10_31_1","DOI":"10.1093\/nar\/gkac1052"},{"unstructured":"Van Camp G.andSmith R. J. H.(2023).Hereditary Hearing Loss Homepage.https:\/\/hereditaryhearingloss.org","key":"e_1_2_10_32_1"},{"doi-asserted-by":"publisher","key":"e_1_2_10_33_1","DOI":"10.1093\/nar\/gkab1061"},{"doi-asserted-by":"publisher","key":"e_1_2_10_34_1","DOI":"10.1002\/lio2.829"},{"doi-asserted-by":"publisher","key":"e_1_2_10_35_1","DOI":"10.1016\/j.ajhg.2018.05.011"},{"doi-asserted-by":"publisher","key":"e_1_2_10_36_1","DOI":"10.1007\/978-3-319-24277-4"},{"doi-asserted-by":"publisher","key":"e_1_2_10_37_1","DOI":"10.1016\/j.jpeds.2023.113620"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63530","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T13:57:57Z","timestamp":1747317477000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63530"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,10]]},"references-count":36,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1002\/ajmg.a.63530"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63530","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"type":"print","value":"1552-4825"},{"type":"electronic","value":"1552-4833"}],"subject":[],"published":{"date-parts":[[2024,1,10]]},"assertion":[{"value":"2023-10-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e63530"}}