Clinical Characteristics and In Vitro Analysis of MYO6 Variants Causing Late-Onset Progressive Hearing Loss.

Genes
Shin-Ichiro OkaShin-Ichi Usami

Abstract

MYO6 is known as a genetic cause of autosomal dominant and autosomal recessive inherited hearing loss. In this study, to clarify the frequency and clinical characteristics of hearing loss caused by MYO6 gene mutations, a large-scale genetic analysis of Japanese patients with hearing loss was performed. By means of massively parallel DNA sequencing (MPS) using next-generation sequencing for 8074 Japanese families, we found 27 MYO6 variants in 33 families, 22 of which are novel. In total, 2.40% of autosomal dominant sensorineural hearing loss (ADSNHL) in families in this study (32 out of 1336) was found to be caused by MYO6 mutations. The present study clarified that most cases showed juvenile-onset progressive hearing loss and their hearing deteriorated markedly after 40 years of age. The estimated hearing deterioration was found to be 0.57 dB per year; when restricted to change after 40 years of age, the deterioration speed was accelerated to 1.07 dB per year. To obtain supportive evidence for pathogenicity, variants identified in the patients were introduced to MYO6 cDNA by site-directed mutagenesis and overexpressed in epithelial cells. They were then assessed for their effects on espin1-induced microvilli formation. Cells wi...Continue Reading

References

Oct 1, 1994·The Journal of Cell Biology·T Hasson, M S Mooseker
Jun 16, 1997·The Journal of Cell Biology·T HassonD P Corey
Oct 16, 1999·Nature·A L WellsH L Sweeney
Oct 20, 1999·Developmental Biology·T SelfK P Steel
Nov 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·R S RockH L Sweeney
May 29, 2002·Proceedings of the National Academy of Sciences of the United States of America·Tom WalshKaren B Avraham
Apr 11, 2003·American Journal of Human Genetics·Zubair M AhmedEdward R Wilcox
Aug 2, 2003·Journal of Cell Science·Tama Hasson
Dec 6, 2003·The Journal of Cell Biology·Patricia A LoomisJames R Bartles
May 19, 2006·The New England Journal of Medicine·Cynthia C Morton, Walter E Nance
Mar 19, 2008·American Journal of Medical Genetics. Part a·Kirsten M SanggaardLisbeth Tranebjaerg
Oct 10, 2013·European Journal of Human Genetics : EJHG·Zippora BrownsteinKaren B Avraham
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Mar 20, 2015·The Annals of Otology, Rhinology, and Laryngology·Shin-Ya Nishio, Shin-Ichi Usami
Dec 22, 2016·European Journal of Human Genetics : EJHG·Celia Zazo SecoHelger G Yntema
Apr 22, 2018·Gene·Alessandro PecciRobert S Adelstein
Jan 23, 2019·Hearing Research·Hannie Kremer

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Citations

May 15, 2021·Scientific Reports·Dominika OziębłoMonika Ołdak
Jun 27, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yuanyuan XueYilai Shu

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Methods Mentioned

BETA
PCR
targeted mutations

Software Mentioned

Torrent Mapping Alignment Program
ImageJ
Torrent Variant Caller
ANNOVAR

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