Novel MYO15A variants are associated with hearing loss in the two Iranian pedigrees

Somayeh Khatami,Saeed Hematian,Masomeh Askari,Fatemeh Bahreini,Morteza Hashemzadeh-Chaleshtori,Samira Asgharzade

doi:10.1186/s12881-020-01168-x

Abstract

BackgroundClinical genetic diagnosis of non-syndromic hearing loss (NSHL) is quite challenging. With regard to its high heterogeneity as well as large size of some genes, it is also really difficult to detect causative mutations using traditional approaches. One of the recent technologies called whole-exome sequencing (WES) has been thus developed in this domain to remove the limitations of conventional methods.MethodsThis study was a report on a research study of two unrelated pedigrees with multiple affected cases of hearing loss (HL). Accordingly, clinical evaluations and genetic analysis were performed in both families.ResultsThe results of WES data analysis to uncover autosomal recessive non-syndromic hearing loss (ARNSHL) disease-causing variants was reported in the present study. Initial analysis identified two novel variants of MYO15A i.e. c.T6442A:p.W2148R and c.10504dupT:p.C3502Lfs*15 correspondingly which were later confirmed by Sanger validations and segregation analyses. According to online prediction tools, both identified variants seemed to have damaging effects.ConclusionIn this study, whole exome sequencing were used as a first approach strategy to identify the two novel variants in MYO15A in two Iranian families with ARNSHL.

Highlights

Clinical genetic diagnosis of non-syndromic hearing loss (NSHL) is quite challenging
; due to the wide variety of pathogenic genes associated with nonsyndromic hearing loss (NSHL), including both nuclear and mitochondrial ones, the disease includes diverse patterns of inheritance comprised of autosomal
Khatami et al BMC Medical Genetics (2020) 21:226 as nuclear modifier genes can render the molecular diagnosis of autosomal recessive non-syndromic hearing loss (ARNSHL) as a challenge [3, 4]

Summary

Introduction

Clinical genetic diagnosis of non-syndromic hearing loss (NSHL) is quite challenging. Hearing impairment is considered as an etiologically heterogeneous sensory deficiency with incidence 1 in 1000 newborns around the world [1]. In this regard, genetic hearing loss (HL) has been divided into syndromic and non-syndromic types. Considering the high rate of consanguineous marriages in the Middle East, autosomal recessive non-syndromic hearing loss (ARNSHL) is reportedly more prevalent western countries [2]. Molecular genetic testing on the basis of multi-gene screening such as whole-exome sequencing (WES) are being used instead of traditional diagnostic procedures [7]

Methods

Results

Discussion

Conclusion