SHERP

Expansion of phenotypic spectrum of MYO15A pathogenic variants to include postlingual onset of progressive partial deafness

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Authors
Chang, Mun Young; Lee, Chung; Han, Jin Hee; Kim, Min Young; Park, Hye-Rim; Kim, Nayoung; Park, Woong-Yang; Oh, Doo Yi; Choi, Byung Yoon
Issue Date
2018-02-27
Publisher
BioMed Central
Citation
BMC Medical Genetics, 19(1):29
Keywords
MYO15APhenotypeDeafnessPathogenic variant
Abstract
Abstract

Background
MYO15A variants, except those in the N-terminal domain, have been shown to be associated with congenital or pre-lingual severe-to-profound hearing loss (DFNB3), which ultimately requires cochlear implantation in early childhood. Recently, such variants have also been shown to possibly cause moderate-to-severe hearing loss. Herein, we also demonstrate that some MYO15A mutant alleles can cause postlingual onset of progressive partial deafness.


Methods
Two multiplex Korean families (SB246 and SB224), manifesting postlingual, progressive, partial deafness in an autosomal recessive fashion, were recruited. Molecular genetics testing was performed in two different pipelines, in a parallel fashion, for the SB246 family: targeted exome sequencing (TES) of 129 known deafness genes from the proband and whole exome sequencing (WES) of all affected subjects. Only the former pipeline was performed for the SB224 family. Rigorous bioinformatics analyses encompassing structural variations were executed to investigate any causative variants.


Results
In the SB246 family, two different molecular diagnostic pipelines provided exactly the same candidate variants: c.5504G > A (p.R1835H) in the motor domain and c.10245_10247delCTC (p.S3417del) in the FERM domain of MYO15A. In the SB224 family, c.9790C > T (p.Q3264X) and c.10263C > G (p.I3421M) in the FERM domain were detected as candidate variants.


Conclusions
Some recessive MYO15A variants can cause postlingual onset of progressive partial deafness. The phenotypic spectrum of DFNB3 should be extended to include such partial deafness. The mechanism for a milder phenotype could be due to the milder pathogenic potential from hypomorphic alleles of MYO15A or the presence of modifier genes. This merits further investigation.
ISSN
1471-2350
Language
English
URI
http://hdl.handle.net/10371/139626
DOI
https://doi.org/10.1186/s12881-018-0541-9
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College of Medicine/School of Medicine (의과대학/대학원)Otorhinolaryngology (이비인후과학전공)Journal Papers (저널논문_이비인후과학전공)
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