Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort

Guney Bademci; Joseph Foster, 2nd; Nejat Mahdieh; Mortaza Bonyadi; Duygu Duman; F Basak Cengiz; Ibis Menendez; Oscar Diaz-Horta; Atefeh Shirkavand; Sirous Zeinali; Asli Subasioglu; Suna Tokgoz-Yilmaz; Fabiola Huesca-Hernandez; Maria de la Luz Arenas-Sordo; Juan Dominguez-Aburto; Edgar Hernandez-Zamora; Paola Montenegro; Rosario Paredes; Germania Moreta; Rodrigo Vinueza; Franklin Villegas; Santiago Mendoza-Benitez; Shengru Guo; Nazim Bozan; Tulay Tos; Armagan Incesulu; Gonca Sennaroglu; Susan H Blanton; Hatice Ozturkmen-Akay; Muzeyyen Yildirim-Baylan; Mustafa Tekin

doi:10.1038/gim.2015.89

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Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort

Journal article

Open access

Peer reviewed

Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort

Guney Bademci, Joseph Foster, 2nd, Nejat Mahdieh, Mortaza Bonyadi, Duygu Duman, F Basak Cengiz, Ibis Menendez, Oscar Diaz-Horta, Atefeh Shirkavand, Sirous Zeinali, …

Genetics in medicine, Vol.18(4), pp.364-371

2016-04

DOI: https://doi.org/10.1038/gim.2015.89

PMID: 26226137

Abstract

Deafness - genetics

Humans

Genotype

Hearing Loss, Sensorineural - genetics

Genes, Recessive

Deafness - diagnosis

Exome

Hearing Loss, Sensorineural - diagnosis

Ethnic Groups - genetics

Alleles

High-Throughput Nucleotide Sequencing

Mutation

Cohort Studies

Autosomal recessive nonsyndromic deafness (ARNSD) is characterized by a high degree of genetic heterogeneity, with reported mutations in 58 different genes. This study was designed to detect deafness-causing variants in a multiethnic cohort with ARNSD by using whole-exome sequencing (WES). After excluding mutations in the most common gene, GJB2, we performed WES in 160 multiplex families with ARNSD from Turkey, Iran, Mexico, Ecuador, and Puerto Rico to screen for mutations in all known ARNSD genes. We detected ARNSD-causing variants in 90 (56%) families, 54% of which had not been previously reported. Identified mutations were located in 31 known ARNSD genes. The most common genes with mutations were MYO15A (13%), MYO7A (11%), SLC26A4 (10%), TMPRSS3 (9%), TMC1 (8%), ILDR1 (6%), and CDH23 (4%). Nine mutations were detected in multiple families with shared haplotypes, suggesting founder effects. We report on a large multiethnic cohort with ARNSD in which comprehensive analysis of all known ARNSD genes identifies causative DNA variants in 56% of the families. In the remaining families, WES allows us to search for causative variants in novel genes, thus improving our ability to explain the underlying etiology in more families.Genet Med 18 4, 364-371.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.150 Hearing Loss; 1.150.421 Cochlea
Web Of Science research areas: Genetics & Heredity
ESI research areas: Clinical Medicine

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Title: Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort
Creators: Guney Bademci - Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA
Joseph Foster, 2nd - Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA
Nejat Mahdieh - Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
Mortaza Bonyadi - Faculty of Natural Sciences, Center of Excellence for Biodiversity, University of Tabriz, Tabriz, Iran
Duygu Duman - Division of Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey
F Basak Cengiz - Division of Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey
Ibis Menendez - Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA
Oscar Diaz-Horta - Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA
Atefeh Shirkavand - Kawsar's Human Genetic Research Center, Tehran, Iran
Sirous Zeinali - Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
Asli Subasioglu - Department of Medical Genetics, Izmir Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey
Suna Tokgoz-Yilmaz - Department of Audiology, Hacettepe University Health Sciences Faculty, Ankara, Turkey
Fabiola Huesca-Hernandez - Genetic Service, National Institute of Rehabilitation, Mexico D.F., Mexico
Maria de la Luz Arenas-Sordo - Genetic Service, National Institute of Rehabilitation, Mexico D.F., Mexico
Juan Dominguez-Aburto - Genetic Service, National Institute of Rehabilitation, Mexico D.F., Mexico
Edgar Hernandez-Zamora - Genetic Service, National Institute of Rehabilitation, Mexico D.F., Mexico
Paola Montenegro - Molecular Genetic Lab, FFAA Hospital, Quito, Ecuador
Rosario Paredes - Molecular Genetic Lab, FFAA Hospital, Quito, Ecuador
Germania Moreta - Molecular Genetic Lab, FFAA Hospital, Quito, Ecuador
Rodrigo Vinueza - Molecular Genetic Lab, FFAA Hospital, Quito, Ecuador
Franklin Villegas - Molecular Genetic Lab, FFAA Hospital, Quito, Ecuador
Santiago Mendoza-Benitez - Audiology Department, Cuernavaca General Hospital, Morelos, Mexico
Shengru Guo - Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA
Nazim Bozan - Department of Otolaryngology, Faculty of Medicine, Yuzuncu Yıl University, Van, Turkey
Tulay Tos - Department of Medical Genetics, Dr. Sami Ulus Research and Training Hospital of Women's and Children's Health and Diseases, Ankara, Turkey
Armagan Incesulu - Department of Otolaryngology, Head and Neck Surgery, Eskisehir Osmangazi University, Eskisehir, Turkey
Gonca Sennaroglu - Department of Audiology, Hacettepe University Health Sciences Faculty, Ankara, Turkey
Susan H Blanton - Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA
Hatice Ozturkmen-Akay - Department of Radiology, Istanbul Zeynep Kamil Maternity and Children Training and Research Hospital, Istanbul, Turkey
Muzeyyen Yildirim-Baylan - Department of Otorhinolaryngology, Dicle University School of Medicine, Diyarbakir, Turkey
Mustafa Tekin - Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA
Publication Details: Genetics in medicine, Vol.18(4), pp.364-371
Publisher: United States
Grant note: R01 DC009645 / NIDCD NIH HHS R01DC009645 / NIDCD NIH HHS
Academic Unit: UMMG Dept of Human Genetics (Dr. John T. Macdonald Foundation); Miller School of Medicine; John P. Hussman Institute for Human Genomics; UMMG Dept of Human Genetics - Clinical and Translational Genetics
Language: English
Resource Type: Journal article
PMID: 26226137
Record Identifier: 991031560143602976