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.
Highlights
Hearing loss (HL) is the most frequent sensory deficit with an incidence of 0.1–0.2% within the newborn population
Considering only the 41 autosomal recessive nonsyndromic hearing loss (ARNSHL) genes included in TruSightTM Exome the percentage of mappable bases representing by a coverage of at least 1X, 10X and 20X reads were 99.80%, 99.60% and 98.90%, respectively
A targeted next generation sequencing (TNGS) panel including known ARNSHL genes has been used to define the genetic etiology in a group of individuals with autosomal recessive NSHL, all recipients of cochlear implants
Summary
Hearing loss (HL) is the most frequent sensory deficit with an incidence of 0.1–0.2% within the newborn population. Genetic causes are the most important etiological factors leading to HL. Hereditary hearing loss (HHL) can be syndromic (SHL) (25%) or nonsyndromic (NSHL)(75%). While SHL is accompanied by other systemic manifestations, in the non-syndromic form (NSHL), there are no additional findings [1, 2]. Depending on the age of onset and severity of HL, HHL is classified as congenital, prelingual, and postlingual, and mild to profound, respectively. The genetic transmission of NSHL is autosomal recessive in 75–85% of all cases (ARNSHL), and autosomal dominant in 15–25% of cases (ADNSHL). Small proportion of cases show Xlinked or mitochondrial inheritance (1–2%)[3]
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