Targeted Genomic Capture And Massive Parallel Sequencing In The Identification Of Causative Variants In Hereditary Hearing Loss

Objective:To explore the application of targeted genomic capture combined with massive parallel sequencing (MPS) in the identification of causative variants in hereditary hearing loss family.Methods:We developed a method for the simultaneous detection of101genes associated with hereditary hearing loss and deafness-related mitochondrial and microRNA regions using targeted genomics capture and MPS. With the technique, genetic analysis of two Chinese families (JSNY-053and JSNY-027) with autosomal progressive sensorineural hearing loss was conducted.Reaults:In JSNY-053Family, a previously reported deafness-related missense mutation (c.1714G>A, p.D572N) was identified in TMC1gene. Meanwhile, a novel missense mutation (c.113G>A, p.G38>D) in the third exon of COCH gene was identified in JSNY-027Family. These two mutations are completely cosegregated with the clinical phenotype of hearing loss. The novel p.38D mutation was predicted to be probably damaging and the mutated protein altered the first turn of LCCL of domain in Gly38.Conclusion:Critical gene mutations could be identified in hereditary hearing loss families accurately and quickly by targeted genomic capture and MPS. The technique will contribute to early clinical diagnosis of hearing loss in the future.