title: Comprehensive Analysis of Deafness Genes in Families with Autosomal Recessive Nonsyndromic Hearing Loss.
abstract: Comprehensive genetic testing has the potential to become the standard of care for individuals with hearing loss. In this study, we investigated the genetic etiology of autosomal recessive nonsyndromic hearing loss (ARNSHL) in a Turkish cohort including individuals with cochlear implant, who had a pedigree suggestive of an autosomal recessive inheritance. A workflow including prescreening of GJB2 and a targeted next generation sequencing panel (Illumına TruSightTM Exome) covering 2761 genes that we briefly called as mendelian exome sequencing was used. This panel includes 102 deafness genes and a number of genes causing Mendelian disorders. Using this approach, we identified causative variants in 21 of 29 families. Three different GJB2 variants were present in seven families. Remaining 14 families had 15 different variants in other known NSHL genes (MYO7A, MYO15A, MARVELD2, TMIE, DFNB31, LOXHD1, GPSM2, TMC1, USH1G, CDH23). Of these variants, eight are novel. Mutation detection rate of our workflow is 72.4%, confirming the usefulness of targeted sequencing approach in NSHL.
authors.affiliation: Division of Pediatric Genetics, Department of Pediatrics, School of Medicine, Ege University, Izmir, Turkey.
authors.forename: Tahir
authors.initials: T
authors.lastname: Atik
authors.affiliation: Department of Medical Genetics, School of Medicine, Ege University, Izmir, Turkey.
authors.forename: Huseyin
authors.initials: H
authors.lastname: Onay
authors.affiliation: Department of Medical Genetics, School of Medicine, Ege University, Izmir, Turkey.
authors.forename: Ayca
authors.initials: A
authors.lastname: Aykut
authors.affiliation: Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, United States of America.
authors.forename: Guney
authors.initials: G
authors.lastname: Bademci
authors.affiliation: Department of Otolarynghology, School of Medicine, Ege University, Izmir, Turkey.
authors.forename: Tayfun
authors.initials: T
authors.lastname: Kirazli
authors.affiliation: Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, United States of America.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Tekin
authors.affiliation: Division of Pediatric Genetics, Department of Pediatrics, School of Medicine, Ege University, Izmir, Turkey.|Department of Medical Genetics, School of Medicine, Ege University, Izmir, Turkey.
authors.forename: Ferda
authors.initials: F
authors.lastname: Ozkinay
mesh_terms: D001483:Base Sequence; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics; D003638:Deafness / Q000175:diagnosis / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26