Identification of Novel Compound Heterozygous MYO15A Mutations in Two Chinese Families with Autosomal Recessive Nonsyndromic Hearing Loss.

Xiao-Hui Wang,Le Xie,Xue Bai,Yu Sun,Yue Qiu,Wei-Jia Kong,Kai Xu,Yuan Jin,Sen Chen,Xiao-Zhou Liu,Geng Lin Li

doi:10.1155/2021/9957712

Xiao-Hui Wang, Le Xie + Show 9 more

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https://doi.org/10.1155/2021/9957712

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Abstract

Congenital deafness is one of the most common causes of disability in humans, and more than half of cases are caused by genetic factors. Mutations of the MYO15A gene are the third most common cause of hereditary hearing loss. Using next-generation sequencing combined with auditory tests, two novel compound heterozygous variants c.2802_2812del/c.5681T>C and c.5681T>C/c.6340G>A in the MYO15A gene were identified in probands from two irrelevant Chinese families. Auditory phenotypes of the probands are consistent with the previously reported for recessive variants in the MYO15A gene. The two novel variants, c.2802_2812del and c.5681T>C, were identified as deleterious mutations by bioinformatics analysis. Our findings extend the MYO15A gene mutation spectrum and provide more information for rapid and precise molecular diagnosis of congenital deafness.

Highlights

Congenital deafness is one of the most common birth defects, with an incidence of approximately 1.4 per 1000 newborns screened
Hair cells (HCs) in the inner ear contribute to transducing sound waves into electric signals [17,18,19,20,21]
Congenital hearing loss could be caused by genetic factors, cochlear infections, ototoxic drugs, and noise exposure, and genetic factors account for more than 60% of congenital hearing loss [22]

Summary

Introduction

Congenital deafness is one of the most common birth defects, with an incidence of approximately 1.4 per 1000 newborns screened. More than 60% of neonates with congenital deafness can be attributable to genetic factors [1] Most of these cases are nonsyndromic hearing loss (NSHL), and autosomal recessive inheritance accounts for up to 80% of NSHL [2]. The MYO15A gene spans 71 kb of genomic DNA on chromosome 17p11.2 It contains 66 exons and encodes unconventional myosin-XV protein which is composed of 3530 amino acids [6]. The protein it encodes mainly localizes in the tips of mammalian hair cell stereocilia, which plays a crucial role in the development of stereocilia and the formation of normal auditory function [7, 8]. The mutation in the motor domain results shorter stereocilia with an abnormal staircase structure which leads to deafness [4]

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