Variants in CDH23 cause a broad spectrum of hearing loss: from non-syndromic to syndromic hearing loss as well as from congenital to age-related hearing loss

Variants in the CDH23 gene are known to be responsible for both syndromic hearing loss (Usher syndrome type ID: USH1D) and non-syndromic hearing loss (DFNB12). Our series of studies demonstrated that CDH23 variants cause a broad range of phenotypes of non-syndromic hearing loss (DFNB12); from congenital profound hearing loss to late-onset high-frequency-involved progressive hearing loss. In this study, based on the genetic and clinical data from more than 10,000 patients, the mutational spectrum, clinical characteristics and genotype/phenotype correlations were evaluated. The present results reconfirmed that the variants in CDH23 are an important cause of non-syndromic sensorineural hearing loss. In addition, we showed that the mutational spectrum in the Japanese population, which is probably representative of the East Asian population in general, as well as frequent CDH23 variants that might be due to some founder effects. The present study demonstrated CDH23 variants cause a broad range of phenotypes, from non-syndromic to syndromic hearing loss as well as from congenital to age-related hearing loss. Genotype (variant combinations) and phenotype (association with retinal pigmentosa, onset age) are shown to be well correlated and are thought to be related to the residual function defined by the CDH23 variants. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00439-022-02431-2.