Molecular diagnosis of non-syndromic hearing loss patients using a stepwise approach

BackgroundHearing loss is one of the most common birth disorders in humans with an estimated prevalence of 1-3 in every 1000 newborns. This study has investigated the molecular etiology of a deaf cohort using a stepwise strategy to effectively diagnose patients and the challenges faced to verify genetic heterogenicity and the variable mutation spectrums of hearing loss.MethodsIn order to target known pathogenic variants, multiplex PCR plus next-generation sequencing was applied in the first tier, while undiagnosed cases were further referred to exome sequencing. A total of 92 unrelated patients with nonsyndromic hearing loss were enrolled.ResultsIn total, 64% (59/92) of patients were molecularly diagnosed, 44 of which were identified in the first tier by multiplex PCR plus sequencing. Of 48 undiagnosed patients from the first tier, exome sequencing identified eleven diagnoses (23%, 11/48) and four probably diagnoses (8%, 4/48). The rate of secondary findings of exome sequencing in our cohort is 3.4%.ConclusionThe research presented a molecular diagnosis spectrum of 92 non-syndromic hearing loss patients and demonstrated the benefits of using the stepwise diagnostic approach in the genetic test of the non-syndromic hearing loss patient cohort.