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.