1. Spectrum of genes for inherited hearing loss in the Israeli Jewish population, including the novel human deafness gene<scp>ATOH1</scp>
- Author
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Tom Walsh, Silvia Casadei, Ofer Isakov, Mary Claire King, Matthew W. Kelley, Noa Ruhrman-Shahar, Eiríkur Steingrímsson, Maria Birkan, Mor Bordeynik-Cohen, Ronna Hertzano, Nadra Samra, Morad Khayat, Nada Danial-Farran, Naama Zvi, Zippora Brownstein, Moshe Frydman, Elon Pras, Ophir Handzel, Moien Kanaan, Fabio Tadeu Arrojo Martins, Michal Macarov, Noam Shomron, Asgeir O. Arnthorsson, Bella Davidov, Doaa Ali-Naffaa, Michal Sagi, Lara Kamal, Reuven Sharony, Lina Basel-Salmon, Ming K. Lee, Meirav Sokolov, Weise Chang, Ory Madgar, Michael Wolf, Dorit Lev, Karen B. Avraham, Hagit Baris-Feldman, Dror Gilony, Ryan J. Carlson, Hana Poran, Noga Lipschitz, Shahar Taiber, Suleyman Gulsuner, Amal Abu-Rayyan, Stavit Allon-Shalev, Chana Vinkler, Amihood Singer, Amir Peleg, Efrat Sofrin‐Drucker, and Mordechai Shohat
- Subjects
Adult ,Male ,0301 basic medicine ,Adolescent ,Hearing loss ,Genetic counseling ,Population ,Genomics ,Deafness ,030105 genetics & heredity ,Biology ,Article ,Young Adult ,03 medical and health sciences ,Genotype ,Basic Helix-Loop-Helix Transcription Factors ,otorhinolaryngologic diseases ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Israel ,Allele ,Child ,Hearing Loss ,education ,Genetic Association Studies ,Genetics (clinical) ,Newborn screening ,education.field_of_study ,Massive parallel sequencing ,Pedigree ,030104 developmental biology ,Child, Preschool ,Jews ,Female ,medicine.symptom - Abstract
Mutations in more than 150 genes are responsible for inherited hearing loss, with thousands of different, severe causal alleles that vary among populations. The Israeli Jewish population includes communities of diverse geographic origins, revealing a wide range of deafness-associated variants and enabling clinical characterization of the associated phenotypes. Our goal was to identify the genetic causes of inherited hearing loss in this population, and to determine relationships among genotype, phenotype, and ethnicity. Genomic DNA samples from informative relatives of 88 multiplex families, all of self-identified Jewish ancestry, with either non-syndromic or syndromic hearing loss, were sequenced for known and candidate deafness genes using the HEar-Seq gene panel. The genetic causes of hearing loss were identified for 60% of the families. One gene was encountered for the first time in human hearing loss: ATOH1 (Atonal), a basic helix-loop-helix transcription factor responsible for autosomal dominant progressive hearing loss in a five-generation family. Our results demonstrate that genomic sequencing with a gene panel dedicated to hearing loss is effective for genetic diagnoses in a diverse population. Comprehensive sequencing enables well-informed genetic counseling and clinical management by medical geneticists, otolaryngologists, audiologists, and speech therapists and can be integrated into newborn screening for deafness.
- Published
- 2020
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