{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T11:00:46Z","timestamp":1780398046683,"version":"3.54.1"},"reference-count":61,"publisher":"Wiley","issue":"2-3","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      In recent years, numerous genetic variants have been linked with prelingual hearing loss (HL). Variants in the\n                      <jats:italic>LOXHD1<\/jats:italic>\n                      gene (lipoxygenase homology domain\u20141) associated with\n                      <jats:italic>DFNB<\/jats:italic>\n                      77 are highly heterogeneous, with different auditory characteristics varying from stable to progressive and mild to profound. To date, 168\n                      <jats:italic>DFNB<\/jats:italic>\n                      77 cases have been recorded worldwide. Forty\u2010one hearing\u2010impaired (HI) probands, who were previously excluded for a set of four common deafness\u2010causing genes (viz.\n                      <jats:italic>, GJB2, GJB6, SLC26A4<\/jats:italic>\n                      , and\n                      <jats:italic>CDH23)<\/jats:italic>\n                      from 33 HI families, were subjected to clinical exome sequencing (CES) involving 285 genes associated with HL. This was followed by a segregation analysis of the available members in the family. We identified two pathogenic\n                      <jats:italic>LOXHD1<\/jats:italic>\n                      variants in two unrelated inbred families. One is a novel homozygous pathogenic nonsense variant (c.3999C\u00a0&gt;\u00a0A; p.C1333X), whereas the other is a likely pathogenic missense variant (c.6046G\u00a0&gt;\u00a0T; p.E2046K). In silico tools such as SIFT, PolyPhen\u20102, Mutation Taster, CADD, and REVEL scores were used to predict variant pathogenicity. Furthermore, American College of Medical Genetics and Genomics guidelines specific to HL were applied to finally classify a variant as pathogenic or otherwise. The frequency of\n                      <jats:italic>LOXHD1 variants<\/jats:italic>\n                      identified in our study is 4.88% (2\/41). This is the first\n                      <jats:italic>LOXHD1<\/jats:italic>\n                      report associated with non\u2010syndromic HL in South Indian families.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ahg.12593","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T06:23:03Z","timestamp":1741760583000},"page":"114-125","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clinical Exome Sequencing Identifies, Two Homozygous\n                    <i>LOXHD1<\/i>\n                    Variants in Two Inbred Families With Pre\u2010Lingual Hearing Loss From South India"],"prefix":"10.1111","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4161-6447","authenticated-orcid":false,"given":"Mathuravalli","family":"Krishnamoorthy","sequence":"first","affiliation":[{"name":"Department of Genetics, Post Graduate Institute of Basic Medical Sciences University of Madras (Taramani Campus)  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3194-2650","authenticated-orcid":false,"given":"Chandru","family":"Jayasankaran","sequence":"additional","affiliation":[{"name":"Department of Genetics, Post Graduate Institute of Basic Medical Sciences University of Madras (Taramani Campus)  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sorna","family":"Lakshmi","sequence":"additional","affiliation":[{"name":"Department of Genetics, Post Graduate Institute of Basic Medical Sciences University of Madras (Taramani Campus)  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chodisetty","family":"Sarvani","sequence":"additional","affiliation":[{"name":"Department of Genetics, Post Graduate Institute of Basic Medical Sciences University of Madras (Taramani Campus)  Chennai Tamil Nadu India"},{"name":"The Gordon Institute of TAFE Geelong  Geelong Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7905-1887","authenticated-orcid":false,"given":"Jeffrey Justin","family":"Margret","sequence":"additional","affiliation":[{"name":"Department of Genetics, Post Graduate Institute of Basic Medical Sciences University of Madras (Taramani Campus)  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subathra","family":"Mahalingam","sequence":"additional","affiliation":[{"name":"Department of Genetics, Post Graduate Institute of Basic Medical Sciences University of Madras (Taramani Campus)  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavithra","family":"Amritkumar","sequence":"additional","affiliation":[{"name":"Department of Genetics, Post Graduate Institute of Basic Medical Sciences University of Madras (Taramani Campus)  Chennai Tamil Nadu India"},{"name":"Meenakshi Academy of Higher Education and Research (MAHER)  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2245-3903","authenticated-orcid":false,"given":"Paridhy Vanniya","family":"Subramanyam","sequence":"additional","affiliation":[{"name":"Department of Genetics, Post Graduate Institute of Basic Medical Sciences University of Madras (Taramani Campus)  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarrath Rathnaraajan","family":"S","sequence":"additional","affiliation":[{"name":"Consultant ENT Surgeon Madras ENT Research Foundation (MERF) Pvt Ltd  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1315-5090","authenticated-orcid":false,"given":"C. 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