A novel missense variant in CEACAM16 gene causes autosomal dominant nonsyndromic hearing loss

Abstract Aim Autosomal dominant non‐syndromic hearing loss is a common sensorineural disorder with extremely high genetic heterogeneity. CEA antigen‐related cell adhesion molecule 16(CEACAM16)is a secreted glycoprotein encoded by the CEACAM16 gene. Mutations in CEACAM16 lead to autosomal dominant non‐syndromic hearing loss in humans, due defects in the tectorial membrane of the inner ear. Here we reported a novel missense variant in CEACAM16 gene causes autosomal dominant non‐syndromic hearing loss. Material and methods A four‐generation Chinese family affected by late‐onset and progressive hearing loss was enrolled in this study. The proband was analyzed by targeted next‐generation sequencing and bioinformatic analysis. And in vitro experiments were performed in overexpressed transfected HEK293T cells to investigate the pathogenesis of the mutant protein. Results We identified a novel missense variant in the CEACAM16 gene c.763A>G; (p.Arg255Gly) as causing autosomal dominant non‐syndromic hearing loss in the Chinese family. Using Western blot analysis, ELISA, and immunofluorescence we found increased expression level of the secreted mutant CEACAM16 protein, both intracellularly and extracellularly, compared with wild type CEACAM16 protein. Conclusion Our study showed that the p.Arg255Gly variant leads to increased secretion of mutant CEACAM16 protein, with potential deleterious effect to the function of the protein. Our findings expand the mutation spectrum of CEACAM16, and further the understanding CEACAM16 function and implications in disease.