title: Spectrum of DNA variants for non-syndromic deafness in a large cohort from multiple continents.
abstract: Hearing loss is the most common sensory deficit in humans with causative variants in over 140 genes. With few exceptions, however, the population-specific distribution for many of the identified variants/genes is unclear. Until recently, the extensive genetic and clinical heterogeneity of deafness precluded comprehensive genetic analysis. Here, using a custom capture panel (MiamiOtoGenes), we undertook a targeted sequencing of 180 genes in a multi-ethnic cohort of 342 GJB2 mutation-negative deaf probands from South Africa, Nigeria, Tunisia, Turkey, Iran, India, Guatemala, and the United States (South Florida). We detected causative DNA variants in 25 % of multiplex and 7 % of simplex families. The detection rate varied between 0 and 57 % based on ethnicity, with Guatemala and Iran at the lower and higher end of the spectrum, respectively. We detected causative variants within 27 genes without predominant recurring pathogenic variants. The most commonly implicated genes include MYO15A, SLC26A4, USH2A, MYO7A, MYO6, and TRIOBP. Overall, our study highlights the importance of family history and generation of databases for multiple ethnically discrete populations to improve our ability to detect and accurately interpret genetic variants for pathogenicity.
authors.affiliation: Department of Otolaryngology (D-48), University of Miami Miller School of Medicine, 1666 NW 12th Avenue, Miami, FL, 33136, USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Yan
authors.affiliation: Department of Otolaryngology (D-48), University of Miami Miller School of Medicine, 1666 NW 12th Avenue, Miami, FL, 33136, USA.
authors.forename: Demet
authors.initials: D
authors.lastname: Tekin
authors.affiliation: Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA.
authors.forename: Guney
authors.initials: G
authors.lastname: Bademci
authors.affiliation: Department of Otolaryngology (D-48), University of Miami Miller School of Medicine, 1666 NW 12th Avenue, Miami, FL, 33136, USA.|Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Foster
authors.affiliation: Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA.
authors.forename: F Basak
authors.initials: FB
authors.lastname: Cengiz
authors.affiliation: Department of Otolaryngology (D-48), University of Miami Miller School of Medicine, 1666 NW 12th Avenue, Miami, FL, 33136, USA.
authors.forename: Abhiraami
authors.initials: A
authors.lastname: Kannan-Sundhari
authors.affiliation: Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA.
authors.forename: Shengru
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Otolaryngology (D-48), University of Miami Miller School of Medicine, 1666 NW 12th Avenue, Miami, FL, 33136, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Mittal
authors.affiliation: Department of Otolaryngology (D-48), University of Miami Miller School of Medicine, 1666 NW 12th Avenue, Miami, FL, 33136, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Zou
authors.affiliation: Department of Otolaryngology (D-48), University of Miami Miller School of Medicine, 1666 NW 12th Avenue, Miami, FL, 33136, USA.
authors.forename: Mhamed
authors.initials: M
authors.lastname: Grati
authors.affiliation: Department of Otorhinolaryngology, Steve Biko Academic Hospital, University of Pretoria, Cnr Malan and Steve Biko Road, Gezina, Pretoria, South Africa.
authors.forename: Rosemary I
authors.initials: RI
authors.lastname: Kabahuma
authors.affiliation: Madras ENT Research Foundation (MERF), No-1, 1st Cross Street, Off. II Main Road, Raja Annamalai Puram, Chennai, 600028, Tamil Nadu, India.
authors.forename: Mohan
authors.initials: M
authors.lastname: Kameswaran
authors.affiliation: Department of Otorhinolaryngology, College of Medicine, University of Ibadan, Ibadan, Nigeria.
authors.forename: Taye J
authors.initials: TJ
authors.lastname: Lasisi
authors.affiliation: Department of Otorhinolaryngology, College of Medicine, University of Ibadan, Ibadan, Nigeria.
authors.forename: Waheed A
authors.initials: WA
authors.lastname: Adedeji
authors.affiliation: Department of Otorhinolaryngology, College of Medicine, University of Ibadan, Ibadan, Nigeria.
authors.forename: Akeem O
authors.initials: AO
authors.lastname: Lasisi
authors.affiliation: Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA.
authors.forename: Ibis
authors.initials: I
authors.lastname: Menendez
authors.affiliation: Institute for Research on Genetic and Metabolic Diseases, INVEGEM, Guatemala City, Guatemala.
authors.forename: Marianna
authors.initials: M
authors.lastname: Herrera
authors.affiliation: Institute for Research on Genetic and Metabolic Diseases, INVEGEM, Guatemala City, Guatemala.
authors.forename: Claudia
authors.initials: C
authors.lastname: Carranza
authors.affiliation: Institute of Biomedical and Clinical Science, University of Exeter Medical School, RILD Wellcome Wolfson Centre, Exeter, UK.
authors.forename: Reza
authors.initials: R
authors.lastname: Maroofian
authors.affiliation: Institute of Biomedical and Clinical Science, University of Exeter Medical School, RILD Wellcome Wolfson Centre, Exeter, UK.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Crosby
authors.affiliation: Laboratoire Procédés de Criblage Moléculaire et Cellulaire, Centre de Biotechnologie de Sfax, Université de Sfax, Sfax, Tunisia.
authors.forename: Mariem
authors.initials: M
authors.lastname: Bensaid
authors.affiliation: Laboratoire Procédés de Criblage Moléculaire et Cellulaire, Centre de Biotechnologie de Sfax, Université de Sfax, Sfax, Tunisia.
authors.forename: Saber
authors.initials: S
authors.lastname: Masmoudi
authors.affiliation: Medical Genetics Laboratory of Genome, Isfahan, Iran.
authors.forename: Mahdiyeh
authors.initials: M
authors.lastname: Behnam
authors.affiliation: Department of Medical Genetics, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Mojarrad
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Division of Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey.
authors.forename: Duygu
authors.initials: D
authors.lastname: Duman
authors.affiliation: Department of Neurobiology, Physiology, and Behavior, Center for Neuroscience, UC Davis, Davis, CA, 95616, USA.|Department of Psychiatry and Behavioral Sciences, Center for Neuroscience, UC Davis, Davis, CA, 95616, USA.
authors.forename: Alex M
authors.initials: AM
authors.lastname: Mawla
authors.affiliation: Department of Neurobiology, Physiology, and Behavior, Center for Neuroscience, UC Davis, Davis, CA, 95616, USA.|Department of Psychiatry and Behavioral Sciences, Center for Neuroscience, UC Davis, Davis, CA, 95616, USA.
authors.forename: Alex S
authors.initials: AS
authors.lastname: Nord
authors.affiliation: Department of Otolaryngology (D-48), University of Miami Miller School of Medicine, 1666 NW 12th Avenue, Miami, FL, 33136, USA.|Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA.|Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
authors.forename: Susan H
authors.initials: SH
authors.lastname: Blanton
authors.affiliation: Department of Otolaryngology (D-48), University of Miami Miller School of Medicine, 1666 NW 12th Avenue, Miami, FL, 33136, USA. xliu@med.miami.edu.|Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA. xliu@med.miami.edu.|Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China. xliu@med.miami.edu.
authors.forename: Xue Z
authors.initials: XZ
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology (D-48), University of Miami Miller School of Medicine, 1666 NW 12th Avenue, Miami, FL, 33136, USA. mtekin@miami.edu.|Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA. mtekin@miami.edu.|Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. mtekin@miami.edu.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Tekin
mesh_terms: D003638:Deafness / Q000453:epidemiology / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D005828:Genetics, Population; D006801:Humans; D008297:Male; D009154:Mutation; D052245:Usher Syndromes / Q000453:epidemiology / Q000235:genetics*