MPZL2 variant analysis with whole exome sequencing in a cohort of Chinese hearing loss patients.

BACKGROUND

Hearing loss is a genetically heterogeneous disease with more than 100 genes identified. Pathogenic variants in the MPZL2 gene cause autosomal recessive non-syndromic hearing loss. MPZL2 patients showed mild to moderate progressive hearing loss with onset age around 10 years old. To date, four pathogenic variants have been identified.

AIMS

To explore the clinical characteristics and variants of MPZL2-related hearing loss, and summarize the prevalence rate in overall hearing loss patients.

MATERIAL AND METHODS

To determine the prevalence of MPZL2-related hearing loss in the Chinese population, we analyzed MPZL2 variants of whole exome sequencing data derived from a cohort of 385 hearing loss patients.

RESULTS

Overall, homozygous MPZL2 variants were identified in 5 sporadic cases (diagnostic rate = 1.30%). A novel missense variant c.52C > T;p.Leu18Phe was identified in one other patient with compound heterozygous mutations in MPZL2, but the pathogenicity was uncertain according to the American College of Medical Genetics guidelines (2015). A patient homozygous for the c.220C > T,p.Gln74Ter variant showed congenital profound hearing loss at all frequencies, a phenotype different from previous reports.

CONCLUSIONS

Our results enriched the mutation and phenotype spectrum of MPZL2-related hearing loss. Comparisons between allele frequencies of MPZL2:c.220C > T;p.Gln74Ter and other common deafness variants suggested that MPZL2:c.220C > T;p.Gln74Ter should be included in the group of common deafness variants for prescreening.