Identification of a Novel Compound Heterozygous Mutation in OTOG in a Chinese Family with Severe Hearing Impairment

Abstract

Objectives: Hearing loss is a worldwide disease. In 50% of the patients, hearing loss is caused by genetic problems associated with GJB2, MTRNR1, SLC26A4, and other genes. Considering the recent development and cost reduction of whole-exome sequencing, it is possible to filter out the normal genes and find which among the more novel genes contributed to the loss of hearing. Methods: After prescreening all individuals for GJB2, MTRNR1 and SLC26A4 mutations, whole-exome sequencing was performed in the proband, and the pathogenic variant was confirmed via Sanger sequencing. Results: The compound-heterozygous variant namely c.8076G>C:p.E2692D and c.6362T>C:p.V2121A in OTOG was identified as a candidate gene of a consanguineous Kazakh family. Conclusion: This is the first reported case of severe deafness caused by an OTOG compound-heterozygous variant in the world and the first case of deafness caused by an OTOG variant in China. This discovery identified the important contribution of OTOG toward deafness and expanded the spectrum of variants responsible for human hearing loss.