Identification of novel MYH14 variants in families with autosomal dominant sensorineural hearing loss

Autosomal dominant sensorineural hearing loss (ADSNHL) is a genetically heterogeneous disorder caused by pathogenic variants in various genes, including MYH14. However, the interpretation of pathogenicity for MYH14 variants remains a challenge due to incomplete penetrance and the lack of functional...

Full description

Saved in:
Bibliographic Details
Published in:American journal of medical genetics. Part A 2024-06, Vol.194 (6), p.e63563-n/a
Main Authors: Duman, Duygu, Ramzan, Memoona, Subasioglu, Asli, Mutlu, Ahmet, Peart, LéShon, Seyhan, Serhat, Guo, Shengru, Ila, Kadri, Balta, Burhan, Kalcioglu, Mahmut Tayyar, Bademci, Guney, Tekin, Mustafa
Format: Article
Language:English
Subjects:
Adolescent
Adult
Child
Exome Sequencing
Female
gene
Genes, Dominant
Genetic Predisposition to Disease
Hearing loss
Hearing Loss, Sensorineural - genetics
Hearing Loss, Sensorineural - pathology
Humans
Male
Middle Aged
Mutation - genetics
MYH14
Myosin Heavy Chains - genetics
Myosin Type II
pathogenic variant
Pathogenicity
Pedigree
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Autosomal dominant sensorineural hearing loss (ADSNHL) is a genetically heterogeneous disorder caused by pathogenic variants in various genes, including MYH14. However, the interpretation of pathogenicity for MYH14 variants remains a challenge due to incomplete penetrance and the lack of functional studies and large families. In this study, we performed exome sequencing in six unrelated families with ADSNHL and identified five MYH14 variants, including three novel variants. Two of the novel variants, c.571G > C (p.Asp191His) and c.571G > A (p.Asp191Asn), were classified as likely pathogenic using ACMG and Hearing Loss Expert panel guidelines. In silico modeling demonstrated that these variants, along with p.Gly1794Arg, can alter protein stability and interactions among neighboring molecules. Our findings suggest that MYH14 causative variants may be more contributory and emphasize the importance of considering this gene in patients with nonsyndromic mainly post‐lingual severe form of hearing loss. However, further functional studies are needed to confirm the pathogenicity of these variants.
ISSN:1552-4825
1552-4833
1552-4833
DOI:10.1002/ajmg.a.63563