by Bong Jik Kim, Ah Reum Kim, Chung Lee, So Young Kim, Nayoung K. D. Kim, Mun Young Chang, Jihye Rhee, Mi-Hyun Park, Soo Kyung Koo, Min Young Kim, Jin Hee Han, Seung-ha Oh, Woong-Yang Park, Byung Yoon Choi
CDH23 mutations have mostly been associated with prelingual severe-to-profound sensorineural hearing loss (SNHL) in either syndromic or nonsyndromic SNHL (DFNB12). Herein, we demonstrate the contribution of
CDH23 mutations to postlingual nonsyndromic SNHL (NS-SNHL). We screened 32 Korean adult probands with postlingual NS-SNHL sporadically or in autosomal recessive fashion using targeted panel or whole exome sequencing. We identified four (12.5%, 4/32) potential postlingual DFNB12 families that segregated the recessive
CDH23 variants, qualifying for our criteria along with rapidly progressive SNHL. Three of the four families carried one definite pathogenic
CDH23 variant previously known as the prelingual DFNB12 variant in a
trans configuration with rare
CDH23 variants. To determine the contribution of rare
CDH23 variants to the postlingual NS-SNHL, we checked the minor allele frequency (MAF) of
CDH23 variants detected from our postlingual NS-SNHL cohort and prelingual NS-SNHL cohort, among the 2040 normal control chromosomes. The allele frequency of these
CDH23 variants in our postlingual cohort was 12.5%, which was significantly higher than that of the 2040 control chromosomes (5.53%), confirming the contribution of these rare
CDH23 variants to postlingual NS-SNHL. Furthermore, MAF of rare
CDH23 variants from the postlingual NS-SNHL group was significantly higher than that from the prelingual NS-SNHL group. This study demonstrates an important contribution of
CDH23 mutations to poslingual NS-SNHL and shows that the phenotypic spectrum of DFNB12 can be broadened even into the presbycusis, depending on the pathogenic potential of variants. We also propose that pathogenic potential of
CDH23 variants and the clinical fate of DFNB12 may be predicted by MAF.
http://ift.tt/2e58bJF
