The prevalence and clinical features of MYO7A-related hearing loss including DFNA11, DFNB2 and USH1B

Abstract

The MYO7A gene is known to be responsible for both syndromic hearing loss (Usher syndrome type1B:USH1B) and non-syndromic hearing loss including autosomal dominant and autosomal recessive inheritance (DFNA11, DFNB2). However, the prevalence and detailed clinical features of MYO7A-associated hearing loss across a large population remain unclear. In this study, we conducted next-generation sequencing analysis for a large cohort of 10,042 Japanese hearing loss patients. As a result, 137 patients were identified with MYO7A-associated hearing loss so that the prevalence among Japanese hearing loss patients was 1.36%. We identified 70 disease-causing candidate variants in this study, with 36 of them being novel variants. All variants identified in autosomal dominant cases were missense or in-frame deletion variants. Among the autosomal recessive cases, all patients had at least one missense variant. On the other hand, in patients with Usher syndrome, almost half of the patients carried biallelic null variants (nonsense, splicing, and frameshift variants). Most of the autosomal dominant cases showed late-onset progressive hearing loss. On the other hand, cases with autosomal recessive inheritance or Usher syndrome showed congenital or early-onset hearing loss. The visual symptoms in the Usher syndrome cases developed between age 5-15, and the condition was diagnosed at about 6-15 years of age.

Figure 1

Onset age of hearing loss in patients with (A) DFNA11 variants, (B) DFNB2 variants, and (C) USH1B variants. There was a tendency for onset age to differ depending on variant type. About half of the DFNA11 patients developed or became aware their HL in their first or second decade, whereas HL onset in about half was after twenty years of age. Almost all DFNB2 cases showed congenital or early-onset progressive HL. As for USH1B cases, all patients showed congenital or early-onset severe-to-profound HL.

Figure 2

Overlapping audiograms for each age group for each hereditary form. (A) Overlapping audiograms for each age group among DFNA11 patients showed progressive HL that gradually worsened from mild-to-moderate and high-frequency sloping HL to flat-type severe-to-profound HL. For (B) DFNB2 cases, their overlapping audiograms also showed progressive HL and about half of the cases over 30 years of age showed severe-to-profound HL. (C) USH1B patients showed congenital severe-to-profound HL.

Figure 3

Hearing threshold of patients with/without CI/EAS for each hereditary form. DFNA11, DFNB2, and USH1B. CI/EAS showed good outcomes for patients with MYO7A variants. The corresponding two groups were tested by t test.