Genetic analysis of CLDN14 in the Chinese population affected with non-syndromic hearing loss.

OBJECTIVE: The CLDN14 gene, encoding the tight junction protein Claudin-14, has been proposed as a candidate causative gene affecting autosomal recessive non-syndromic hearing loss (ARNSHL). Genetic analysis of nonsynonymous single-nucleotide variations (nsSNVs) in CLDN14 has been performed in different populations. The role of CLDN14 nsSNVs in contributing to hearing loss in Chinese populations would be investigated in this study.

METHODS: Target screening for CLDN14 variations were conducted in 500 unrelated patients diagnosed with non-syndromic hearing loss (NSHL).

RESULTS: No reported pathogenic CLDN14 nsSNVs in heterozygote or homozygote were detected in this study, however, we identified 4 heterozygous nsSNVs [c.11C > T, p.(Thr4Met); c.16G > A, p.(Val6Met); c.68T > C, p.(Ile23Thr); c.367A > C, p.(Thr123Pro)] in CLDN14. The 4 nsSNVs are located at claudin-14 transmembrane domains, but assessed to be poorly conservative and non-pathogenic via multiple in silico algorithms. The structure-based analysis also suggested that the 4 nsSNVs had less structural and functional impact on claudin-14.

CONCLUSION: Our findings indicated that CLDN14 might not be a major causative gene for NSHL in Chinese populations, which would contribute to fully understanding the genetic cause of NSHL in the East Asian populations.