A novel duplication mutation in the MYO7A gene associated with autosomal recessive hearing loss in a Chinese family.

BACKGROUND: Hearing loss (HL) is one of the most common sensory defects with genetic and environmental etiologies, which is classified into syndromic and non-syndromic hearing loss (NSHL). Variants in MYO7A have been found to result in non-syndromic hearing loss (DFNB2, DFNA11) and Usher Syndrome type 1B (USH1B). However, only a small number of variants result in DFNB2. OBJECTIVE: To explore the pathogenic variant for a Chinese pedigree with autosomal recessive hearing loss (ARNSHL). METHODS: The clinical characteristics of the Chinese family were mainly showed by the audiological and ocular examinations. Exome sequencing and Sanger sequencing were utilized to identify the causative variant of the Chinese pedigree with ARNSHL, followed by molecular modeling analysis of effect of the variant on the protein function. RESULTS: The affected patients currently simply exhibited symmetrical bilateral severe-to-profound neurosensory deafness at all frequencies without vestibular dysfunction or retinitis pigmentosa. We identified a novel duplication variant c.275_278dupACCT in the MYO7A gene using exome sequencing, which was further confirmed by Sanger sequencing. This homozygous variant was co-segregated with the ARNSHL phenotype in this Chinese family. Genetic mutation analysis and molecular modeling function prediction further supported the hypothesis that this novel homozygous variant is pathogenic. CONCLUSION: The novel homozygous variant c.275_278dupACCT (p.Ile94Profs*47) in MYO7A gene is responsible for this Chinese family with ARNSHL. Our results expand the spectrum of MYO7A variants and provide molecular insights into the pathogenesis of NSHL.