Identification of a novel homozygous mutation in MYO3A in a Chinese family with DFNB30 non-syndromic hearing impairment

Ronggui Qu; Qing Sang; Yao Xu; Ruizhi Feng; Li Jin; Lin He; Lei Wang

doi:10.1016/j.ijporl.2016.02.036

Identification of a novel homozygous mutation in MYO3A in a Chinese family with DFNB30 non-syndromic hearing impairment

Int J Pediatr Otorhinolaryngol. 2016 May:84:43-7. doi: 10.1016/j.ijporl.2016.02.036. Epub 2016 Mar 5.

Authors

Ronggui Qu¹, Qing Sang¹, Yao Xu¹, Ruizhi Feng¹, Li Jin², Lin He³, Lei Wang⁴

Affiliations

¹ State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China; Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
² State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
³ Institutes of Biomedical Sciences, Fudan University, Shanghai, China; Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
⁴ State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China; Institutes of Biomedical Sciences, Fudan University, Shanghai, China. Electronic address: wangleiwanglei@fudan.edu.cn.

PMID: 27063751
DOI: 10.1016/j.ijporl.2016.02.036

Abstract

Introduction: Hearing loss is a common sensory impairment. Several genetic loci or genes responsible for non-syndrome hearing loss have been identified, including the well-known deafness genes GJB2, MT-RNR1 and SLC26A4. MYO3A belongs to the myosin superfamily. Previously only three mutations in this gene have been found in an Isreali family with DFNB30, in which patients demonstrated progressive hearing loss.

Methods: In this study, we characterized a consanguineous Kazakh family with congenital hearing loss. By targeted sequence capture and next-generation sequencing, we identified a homozygous mutation and did bioinformatics analysis to this mutation.

Results: A homozygous mutation, MYO3A:c.1841C>T (p.S614F), was identified to be responsible for the disease. Ser614 is located in the motor domain of MYO3A that is highly conserved among different species. Molecular modeling predicts that the conserved Ser614 may play an important role in maintaining the stability of β-sheet and the interaction between neighboring β-strand.

Conclusions: This is the second report on MYO3A mutations in deafness and the first report in China. The finding help facilitate establishing a better relationship between MYO3A mutation and hearing phenotypes.

Keywords: Congenital non-syndromic autosomal recessive deafness; Missense mutation; Myosin IIIA; Target sequencing.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Child, Preschool
China
Consanguinity
Deafness / congenital
Deafness / ethnology
Deafness / genetics*
Female
Genetic Markers
Hearing Loss, Sensorineural / congenital
Hearing Loss, Sensorineural / ethnology
Hearing Loss, Sensorineural / genetics*
Homozygote
Humans
Kazakhstan / ethnology
Male
Mutation, Missense
Myosin Heavy Chains / genetics*
Myosin Type III / genetics*

Substances

Genetic Markers
MYO3A protein, human
Myosin Type III
Myosin Heavy Chains

Supplementary concepts

Deafness, Autosomal Recessive 30
Nonsyndromic Deafness