title: Targeted Resequencing of Deafness Genes Reveals a Founder MYO15A Variant in Northeastern Brazil.
abstract: Identifying the genetic etiology in a person with hearing loss (HL) is challenging due to the extreme genetic heterogeneity in HL and the population-specific variability. In this study, after excluding GJB2 variants, targeted resequencing of 180 deafness-related genes revealed the causative variants in 11 of 19 (58%) Brazilian probands with autosomal recessive HL. Identified pathogenic variants were in MYO15A (10 families) and CLDN14 (one family). Remarkably, the MYO15A p.(Val1400Met) variant was identified in eight families from the city of Monte Santo in the northeast region of Brazil. Haplotype analysis of this variant was consistent with a single founder. No other cases with this variant were detected among 105 simplex cases from other cities of northeastern Brazil, suggesting that this variant is confined to a geographical region. This study suggests that it is feasible to develop population-specific screening for deafness variants once causative variants are identified in different geographical groups.
authors.affiliation: John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.|Gonçalo Moniz Research Center (CPqGM), Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Bahia, Brazil.
authors.forename: Gabrielle N
authors.initials: GN
authors.lastname: Manzoli
authors.affiliation: John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
authors.forename: Guney
authors.initials: G
authors.lastname: Bademci
authors.affiliation: Gonçalo Moniz Research Center (CPqGM), Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Bahia, Brazil.
authors.forename: Angelina X
authors.initials: AX
authors.lastname: Acosta
authors.affiliation: Serviço de Genética Médica, Hospital de Clinicas de Porto Alegre, Brazil.
authors.forename: Têmis M
authors.initials: TM
authors.lastname: Félix
authors.affiliation: John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
authors.forename: F Basak
authors.initials: FB
authors.lastname: Cengiz
authors.affiliation: John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Foster
authors.affiliation: Gonçalo Moniz Research Center (CPqGM), Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Bahia, Brazil.
authors.forename: Danniel S Dias
authors.initials: DS
authors.lastname: Da Silva
authors.affiliation: John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
authors.forename: Ibis
authors.initials: I
authors.lastname: Menendez
authors.affiliation: John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
authors.forename: Isalis
authors.initials: I
authors.lastname: Sanchez-Pena
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
authors.forename: Demet
authors.initials: D
authors.lastname: Tekin
authors.affiliation: John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.|Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.|Dr. John T. Macdonald Foundation 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: Gonçalo Moniz Research Center (CPqGM), Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Bahia, Brazil.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Abe-Sandes
authors.affiliation: John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.|Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
authors.forename: Xue Zhong
authors.initials: XZ
authors.lastname: Liu
authors.affiliation: John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.|Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.|Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Tekin
mesh_terms: D001938:Brazil; D016022:Case-Control Studies; D057167:Claudins / Q000235:genetics; D004252:DNA Mutational Analysis; D018703:Founder Effect; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense; D009218:Myosins / Q000235:genetics*
chemical_list: D057167:Claudins; C485245:MYO15A protein, human; D009218:Myosins; C422064:claudin 14
keywords: Founder; gene; hearing loss; targeted resequencing