Deafness genes in families with non-syndromic hearing loss in Shandong, China: a genetic study.

BACKGROUND: Hearing loss is the most frequent sensory disorder, affecting 1 in 500 newborns. More than 90 genes are associated with non-syndromic hearing loss. In this study we aimed to investigate the genetic etiology of families with non-syndromic hearing loss in Shandong, China.

METHODS: Patients included in this study were sequentially referred to the Otolaryngology Department, Shandong Provincial Hospital. All participants (or their parents) gave informed consent. Individuals with mutations in the most common deafness-associated genes GJB2, SLC26A4 and MT-RNR1 were pre-screened by SNPscan assay. We then did comprehensive clinical genetic testing on the remaining individuals using targeted exon capturing of 173 known deafness genes and massively parallel sequencing.

FINDINGS: We recruited 223 patients (121 men, 102 women; aged 0·5-73 years) from 223 families to this study. We detected deafness gene variants associated with non-syndromic hearing loss in 138 (62%) families, 18% (25/138) of which had not been previously reported. The novel variants in deafness genes were further confirmed by Sanger sequencing in the members of the family and other ethnicity-matched controls. Mutations were found in 17 known genes. The most common genes with mutations were GJB2 (58/138), SLC26A4 (51/138), MT-RNR1 (9/138), MYO15A (3/138), WFS1 (3/138), POU4F3 (2/138), TMC1 (2/138).

INTERPRETATION: We did comprehensive analysis of 173 genes associated with deafness in a large cohort with non-syndromic hearing loss. We identified genetic variants in 62% of the families. Comprehensive genetic testing has the potential to become the standard of care for individuals with hearing loss.

FUNDING: National 973 Basic Research Program of China (2014CB541703).