Application of targeted next-generation sequencing in SNHL patients

Abstract

Sensorineural hearing loss, SNHL, is a complex disease impacted by the interaction of a multitude of endogenous and exogenous factors. Genetic and age-related changes predetermine the state of hearing. Genetic factors and factors affecting development play a key role in the occurrence of SNHL. The goal of this study is to research functioning of the hearing organ in patients with a family history of reduced hearing, to analyse the causes of deafness, to provide an identification strategy of genetic causes and to refer the patient to the most effective treatment.
The study included 192 patients: 178 of them with sensorineural hearing loss and 14 subjects with normal hearing, relatives of the study patients with impaired hearing, of who biological material was also taken to look for mutations associated with hearing. Screening of the patients participating in the study started with searching for mutations in Сх26 (GJB2), Cx30 (GJB6) and Cx31 (GJB3). At the next stage, five families were chosen from the patients without a mutation in the screened genes. They underwent targeted nextgeneration sequencing in search of rare genes causing SNHL. Clinical, audiological and genetic methods were used in conducting the study.
In 31.77% of the cases the reason for deafness was identified (a genetic reason was found) of which 29.69% cases (n= 57) were mutations in Сх26 (in a homozygous state), corresponding with data published in world’s literature on mutations in Сх26 of between 18 to 40% in cases of patients with SNHL. In the remaining 2.08% of the patients, rare mutations responsible for the deafness were identified.