1. Spectrum of genes for inherited hearing loss in the Israeli Jewish population, including the novel human deafness geneATOH1
- Author
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Noam Shomron, Mor Bordeynik-Cohen, Lara Kamal, Dror Gilony, Ryan J. Carlson, Morad Khayat, Asgeir Orn Arnporsson, Tom Walsh, Silvia Casadei, Naama Zvi, Noga Lipschitz, Hana Poran, Michal Sagi, Maria Birkan, Weise Chang, Ory Madgar, Amihood Singer, Shahar Taiber, Ronna Hertzano, Noa Ruhrman-Shahar, Ophir Handzel, Eiríkur Steingrímsson, Moien Kanaan, Michael Wolf, Hagit Baris-Feldman, Amir Peleg, Chana Vinkler, Bella Davidov, Michal Macarov, Stavit Allon-Shalev, Nadra Samara, Ming Lee, Reuven Sharony, Meirav Sokolov, Elon Pras, Karen B. Avraham, Zippora Brownstein, Fabio Tadeu Arrojo Martins, Efrat Sofrin, Matthew W. Kelley, Dorit Lev, Mordechai Shohat, Moshe Frydman, Lina Basel-Salmon, Ofer Isakov, Mary Claire King, Nada Danial-Farran, Amal Abu Rayyan, Suleyman Gulsuner, and Doaa Ali-Naffaa
- Subjects
Genetics ,Newborn screening ,education.field_of_study ,Hearing loss ,Genetic counseling ,Population ,Biology ,Phenotype ,Genotype ,otorhinolaryngologic diseases ,medicine ,Allele ,medicine.symptom ,education ,Gene - 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