{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T11:41:24Z","timestamp":1760960484218,"version":"build-2065373602"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,2,27]],"date-time":"2018-02-27T00:00:00Z","timestamp":1519689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003970","name":"Isfahan University of Medical Sciences","doi-asserted-by":"publisher","award":["194068","295176","394531"],"award-info":[{"award-number":["194068","295176","394531"]}],"id":[{"id":"10.13039\/501100003970","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005001","name":"Ahvaz Jundishapur University of Medical Sciences","doi-asserted-by":"publisher","award":["U\u201091074"],"award-info":[{"award-number":["U\u201091074"]}],"id":[{"id":"10.13039\/501100005001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aao-hnsfjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Otolaryngol.--head neck surg."],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Hearing loss (HL) is the most common sensory\u2010neural defect and the most heterogeneous trait in humans, with the involvement of &gt;100 genes, which make a molecular diagnosis problematic. Next\u2010generation sequencing (NGS) is a new strategy that can overcome this problem.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Descriptive experimental study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Diagnostic laboratory.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects and Methods<\/jats:title><jats:p>A comprehensive family history was obtained, and clinical evaluations and pedigree analysis were performed in a family with multiple individuals with HL. As the first tier, <jats:italic>GJB2<\/jats:italic> was sequenced, and genetic linkage analysis of DFNB1A\/B was performed to rule out the most common cause of the disease. Targeted NGS was used to unravel the molecular etiology of the disease in the HL\u2010associated genes in the proband. Two homozygous variants remained in <jats:italic>OTOF<\/jats:italic> after proper filtration. Cosegregation and in silico analysis were done. Preimplantation genetic diagnosis (PGD) was accomplished via linkage analysis and direct sequencing of the pathogenic variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Clinical evaluations suggested autosomal recessive nonsyndromic HL. Two homozygous variants, c.367G&gt;A (p.Gly123Ser) and c.1392+1G&gt;A, were identified in <jats:italic>cis<\/jats:italic> status. c.1392+1G&gt;A met the criteria for being pathogenic according to the variant interpretation guideline of the American College of Medical Genetics and Genomics. PGD was successfully performed to prevent the recurrence of the disease in the related family.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A novel <jats:italic>OTOF<\/jats:italic> mutation causing HL was identified. Here, we report the effectiveness of the combined application of targeted NGS and PGD in diagnosis and prevention of hereditary HL.<\/jats:p><\/jats:sec>","DOI":"10.1177\/0194599818759007","type":"journal-article","created":{"date-parts":[[2018,2,27]],"date-time":"2018-02-27T08:01:40Z","timestamp":1519718500000},"page":"1084-1092","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Novel Pathologic Variant in <i>OTOF<\/i> in an Iranian Family Segregating Hereditary Hearing Loss"],"prefix":"10.1002","volume":"158","author":[{"given":"Mohammad Amin","family":"Tabatabaiefar","sequence":"first","affiliation":[{"name":"Department of Genetics and Molecular Biology School of Medicine Isfahan University of Medical Sciences Isfahan Iran"},{"name":"Pediatric Inherited Diseases Research Center Research Institute for Primordial Prevention of Noncommunicable Disease Isfahan University of Medical Sciences Isfahan 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