Massively Parallel DNA Sequencing Successfully Identified Seven Families With Deafness-Associated MYO6 Mutations

Abstract

MPS is powerful tool for the identification of rare causative deafness gene mutations, such as MYO6. The clinical characteristics noted in the present study not only confirmed the findings of previous reports but provided important new clinical information.

A clinical guidance to DFNA22 drawn from a Korean cohort study with an autosomal dominant deaf population: A retrospective cohort study

“…This was quite similar to a study evaluating a Caucasian population . Four variants of MYO6 were detected among Japanese deaf subjects and they showed diverse audiogram configurations, including flat and high‐frequency involved with mostly mild to moderate degree HL, except one profound HL patient who eventually received a cochlear implant (CI) . Regarding DFNA22 in Koreans, seven variants of MYO6, including this study, were reported to date, and one variant (c.614G > A, p.R205Q) was shared with a Japanese DFNA22 subject.…”

“…Notably, 60% of our DFNA22 cohort from our institute had a nonsense variant (c.613C > T, p.R205X) occurring at the p.R205 residue. This residue was also previously reported in association with a pathogenic missense variant of p.R205Q in both Korean and Japanese cohorts, of which, a pathogenic effect on actin‐activated ATPase activity was functionally shown . This raised the possibility that this site is susceptible to mutational pressure and thus can be a mutational hotspot rather than a founder allele.…”

“…Hereditary deafness related to MYO6 captures the interest of both clinicians and researchers because it can be either an autosomal dominant (AD)‐ or autosomal recessive (AR)‐inherited disease, representing a wide spectrum of clinical phenotypes in accordance with the studies mentioned above . Moreover, MYO6 was found to significantly contribute to AD‐inherited genetic hearing loss (HL) in the Korean deaf populations, with five novel variants being reported .…”

“…By contrast, audiological phenotypes of DFNB37 caused by recessive MYO6 mutant alleles from three different causative alleles were rather consistent with respect to congenital onset and a degree of at least severe HL . Clarification of genotype–phenotype correlations underlying diverse phenotypes of DFNA22, if any, were pursued; however, variants were distributed along the whole domains of myosin VI and interfamilial or even intrafamilial variation existent under the same variant made it almost impossible to characterize the genotype–phenotype correlation in DFNA22 . Surprisingly, even the same variant, p.R1166X, of MYO6 showed different phenotypes of DFNA22 (mild degree of HL starting in their thirties) and DFNB37 (congenital profound HL) in the Japanese and Pakistani population, respectively .…”

“…the mouse homologue of MYO6 ) is altered, this can cause Snell's Waltzer in mice, which manifests as deafness and vestibular dysfunction . Subsequent to the identification of MYO6 as a deafness gene, 17 variants of DFNA22 and five variants of DFNB37 have been reported …”