The p.R206C Mutation in <b><i>MYO7A</i></b> Leads to Autosomal Dominant Nonsyndromic Hearing Loss

Abstract

Background: Dominant mutations in MYO7A may lead to nonsyndromic deafness DFNA11. A p.R206C variant in MYO7A has previously been reported in a small deaf family from Taiwan but with ambiguous pathogenicity and inheritance pattern. Aims/Objectives: Our study aims to clarify the pathogenicity of this variant by clinical characterization and genetic analysis of a separate autosomal dominant deaf family harboring this variant in mainland China. Materials and Methods: Auditory features of hearing loss were characterized in representative affected family members. Mutation screening was performed by targeted next-generation sequencing of 138 known deafness genes in the proband. Candidate pathogenic mutations were confirmed by Sanger sequencing in family members and ethnically matched controls. Results: Consistent with typical DFNA11 phenotype, the affected family members in this study showed delayed-onset, progressive hearing loss affecting mostly high frequencies. Targeted next-generation sequencing identified a p.R206C mutation in MYO7A as the only candidate pathogenic mutation cosegregating with the hearing phenotype. This mutation is not seen in 200 Chinese Han normal-hearing controls. Conclusions and Significance: The

Clinical Heterogeneity Associated with MYO7A Variants Relies on Affected Domains

“…In this respect, the clinical spectrum of DFNA11 has scarcely been revealed, and little is known about its global or ethnic incidence rates. Since the first report of a 9 bp in-frame deletion variant in the SAH region of a Japanese family, 12 families worldwide have been reported to date [3,[22][23][24][25][26][27][28][29][30][31][32][33][34]. Here, we added six more families with genotypic and phenotypic characteristics of DFNA11.…”

“…Otoscopy, tympanometry, and pure-tone audiometry (PTA) were performed for audiological evaluations. Hearing loss was categorized as mild (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40), moderate (41-55 dBHL), moderate to severe (56-70 dBHL), severe (71-90 dBHL), and profound (>90 dBHL) based on the average PTA threshold across the four frequencies (500, 1000, 2000, and 4000 Hz). The audiogram configuration was characterized as ascending when thresholds for high frequencies (2000 and 4000 Hz) were less by 25 dB than those for low frequencies (250 and 500 Hz), down sloping when low frequencies were less by 25 dB than high frequencies, and flat when the difference between high and low frequencies was within 25 dB.…”