A novel variant in the CDH23 gene is associated with non-syndromic hearing loss in a Chinese family

Objectives: To explore the pathogenic causes of a proband who was diagnosed with non-syndromic hearing loss. Methods: We performed targeted capture of 159 known deafness-related genes and next-generation sequencing in the proband who was tested negative for the twenty hotspot variants in four common deafness-related genes (GJB2, GJB3, SLC26A4 and MTRNRI); Clinical reassessments, including detailed audiological and ocular examinations were performed in the proband and his normal parents. Results: We identified a novel heterozygous variant of CDH23:c.4567A > G (p.Asn1523Asp) in exon 37 (NM_022124), in conjunction with a reported mutation of CDH23:c.5101G > A (p.G1u1701Lys) in exon 40, to be a potentially pathogenic compound heterozygosity in the proband. The unaffected father has a heterozygous variant of CDH23:c.4567A > G, and the normal mother has another heterozygous variant, CDH23:c.5101G > A. The novel variant was absent in the 1000 Genomes Project. The clinical reassessments revealed binaural profound sensorineural hearing loss (DFNB12) without retinitis pigmentosa in the proband. Conclusions: This study demonstrates that the novel variant c.4567A > G (p.Asn1523Asp) in compound heterozygosity with c.5101G > A (p. Glu1701Lys) in the CDH23 gene is the main cause of DFNB12 in the proband. Simultaneously, this study provides a foundation to further elucidate the CDH23-related mechanisms of DFNB12.