A novel missense mutation in SMPX causes a rare form of X-linked postlingual sensorineural hearing loss in a Chinese family.

Background X-linked deafness-4 (DFNX4) caused by the functional loss of the SMPX gene is one form of nonsyndromic hearing loss with postlingual onset. This study aimed to investigate the cause of X-linked inherited sensorineural nonsyndromic hearing loss in a four-generation Chinese family and to explain the reason for extremely different hearing phenotypes between the proband and other family members. Methods Whole-exome sequencing (WES) and co-segregation analysis were used to identify the pathogenic variants. Furthermore, methylation differences among the androgen receptor genes were utilized to investigate whether the severe phenotype of the proband is related to X-chromosome inactivation (Xi). Results We described in detail the clinical characteristics of the family and identified a novel missense mutation (c.262C>G: p.Gln88Glu) in SMPX by WES. This variant was co-segregated with the postlingual hearing loss phenotype and was absent in 300 normal controls. Also, we found that the proband, a 4-year-old female, carries two new compound heterozygous mutations (c.9259G>A: p.Val3087Ile and c.8576G>A: p.Arg2859His) in the USH2A gene, but to date without any other symptoms except profound sensorineural hearing loss. Additionally, analysis of X-chromosome inactivation indicated moderate skewing in the proband, which is probably related to the heterogeneity of clinical characteristics. Conclusions This is the first study to report a missense mutation of SMPX in a Chinese family. Our findings have enriched the mutation and phenotypic spectrum of the SMPX gene.