Abstract
BACKGROUND: Genetic components contribute significantly to the cause of hearing loss. Nonsyndromic hearing loss has been shown to have high genetic heterogeneity. For families who had given birth to two nonsyndromic deaf children in succession, it seems that their deafness was highly related to genetics. OBJECTIVES: This study aimed to disclose the genetic causes of the subjects from the four Chinese families with two nonsyndromic deaf children in succession who failed to find the genetic etiology of the hearing loss by common deafness genetic screening (GJB2, GJB3, SLC26A4, and MT-RNR1, including 20 hot variants in 4 genes). METHODS: Targeted next-generation sequencing (NGS) of 127 known deafness genes was performed in probands of four families, followed by a series of comprehensive analyses of all family members combined with a literature review of related genes. RESULTS: We identified pathogenic variants in three families including c.919-2A>G/c.1985G>A in SLC26A4; c.109G>A (p.V37I) in GJB2; and m.7505T>C in MT-TS1. Sanger sequencing confirmed that these variants segregated with the hearing impairment of each family. We also identified c.331C>T/c.625-5C>T/c.5717G>A in CDH23; c.138T>C in POU3F4 in two families, in which the pathogenicity in clinical was likely pathogenic or unknown. CONCLUSIONS: Using the NGS detection technology, we found the genetic etiology of the HL in part of deaf families. Our study provided a useful piece of information for the variant spectrum of hearing loss in Chinese families with two deaf children in succession.