The audiological phenotype of patients with a variant in MYH9 and MYH14 genes

Abstract

Mutations in MYH9 and MYH14 are associated with autosomal dominant, progressive sensorineural hearing loss. This study aimed to characterize and compare the clinical and audiological features of patients with MYH9 or MYH14 variants. Thirteen patients with MYH9 or MYH14 mutations were identified through whole-exome or targeted sequencing and underwent audiometric evaluations. Both groups exhibited late-onset, high-frequency, progressive hearing loss. The MYH9 group showed a higher proportion of severe-to-profound cases (41.7%) compared to the MYH14 group (14.3%). One MYH14 case presented with congenital hearing loss linked to a nonsense variant (p.Q25*), expanding the phenotypic spectrum of MYH14-related hearing loss. Several novel variants were identified in both genes, all of which were extremely rare and predicted to be deleterious by in silico analyses. Contrary to previous reports, no syndromic features were observed in patients with MYH9 mutations, although one patient had a marginally elevated mean platelet volume. These findings highlight overlapping auditory phenotypes between MYH9 and MYH14 mutations, with particularly marked variability in the genetic and phenotypic features in MYH9. Early genetic diagnosis can aid in prognosis and support individualized management for patients with progressive hearing loss caused by variants in non-muscle myosin genes.

Fig. 1

Audiologic profiles of patients with variants in MYH9 or MYH14. (a) Median pure-tone thresholds at each frequency for patients with MYH9 (blue) and MYH14 (red) variants. Error bars represent interquartile ranges. (b) Correlation between average PTA₄ (Y-axis) and age (X-axis). Each dot represents an individual ear, and the lines represent best-fit regression slopes. (c, d) Pure-tone thresholds at each frequency for all enrolled patients are shown. Each dot represents an individual ear. Dots with the same color indicate the same person, and connected lines represent the same ear. X-axis: Pure-tone frequencies (panels A, C, and D); Y-axis: Pure-tone thresholds (dB HL). The dotted line represents 0 dB HL.

Fig. 2

Segregation analysis in patients with MYH9 variants. Pedigrees, pure-tone audiograms in affected individuals, and segregation analysis from Sanger sequencing for MYH9 variants are depicted in YUHL 107 and YUH 91 families (3 family members included in each family). In pure-tone audiograms, red and blue colors indicate hearing thresholds at right and left ears, respectively.