Spectrum of genes for inherited hearing loss in the Israeli Jewish population, including the novel human deafness gene <scp> <i>ATOH1</i> </scp>
Zippora Brownstein, Süleyman Gülsüner, Tom Walsh, Fábio Tadeu Arrojo Martins, Shahar Taiber, Ofer Isakov, Ming K. Lee, Mor Bordeynik‐Cohen, Maria Birkan, Weise Chang, Silvia Casadei, Nada Danial‐Farran, Amal Abu Rayyan, Ryan J. Carlson, Lara Kamal, Asgeir Ö. Arnthórsson, Meirav Sokolov, Dror Gilony, Noga Lipschitz, Moshe Frydman, Bella Davidov, Michal Macarov, Michal Sagi, Chana Vinkler, Hana Poran, Reuven Sharony, Nadra Nasser Samra, Naama Zvi, Hagit Baris Feldman, Amihood Singer, Ophir Handzel, Ronna Hertzano, Doaa Ali‐Naffaa, Noa Ruhrman‐Shahar, Ory Madgar, Efrat Sofrin‐Drucker, Amir Peleg, Morad Khayat, Mordechai Shohat, Lina Basel‐Vanagaite, Elon Pras, Dorit Lev, Michael Wolf, Eirı́kur Steingrı́msson, Noam Shomron, Matthew W. Kelley, Moien Kanaan, Stavit A. Shalev, Mary‐Claire King, Karen B. Avraham
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 show 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.