Identification of a novel mutation in CRYM in a Chinese family with hearing loss using whole‑exome sequencing

Abstract

Previous studies have identified ~50 genes that contribute to non-syndromic autosomal dominant sensorineural deafness (DFNA). However, in numerous families with hearing loss, the specific gene mutation remains to be identified. In the present study, the clinical characteristics and gene mutations were analyzed in a Chinese pedigree with hereditary hearing loss. The clinical characteristics of the family members were assessed and a detailed audiology function examination was performed. Whole-exome sequencing (WES) was performed to identify the gene mutation responsible for the hearing loss. Sanger sequencing was used to verify the candidate mutation detected in the family. The family consisted of 31 members, seven of whom were diagnosed with sensorineural deafness of varying degrees. No mutation was identified by the general deafness gene chip. However, a novel heterozygous mutation in exon 3 (c.152C>T; Pro51Leu) of the gene crystallin µ (CRYM) was identified by WES. This result was further verified by Sanger sequencing. Co-segregation of genotypes and phenotypes suggested that this novel mutation was instrumental for the hearing loss/DFNA. In conclusion, the present study identified a novel pathogenic mutation, NM_001888.5(CRYM): c.152C>T(Pro51Leu), associated with DFNA. This mutation has not been reported previously and further functional studies are warranted.

µ-Crystallin: A thyroid hormone binding protein

“…A third heterozygous mutation, P51L was later found to associate with DFNA40. This mutation also segregates in an autosomal dominant fashion, further confirming the inheritance pattern of DFNA40 (Wang et al 2020). The severity of hearing loss varies with the mutations noted above.…”

“…Individuals with the K314T show severe bilateral hearing loss (80–90 dB) starting at 1 year old, with no further progression ( Abe et al 2003 ). Individuals with the P51L mutation have moderate to severe hearing loss (50–110 dB) without progression, though only one individual was followed for 4 years ( Wang et al 2020 ).…”