Strong founder effect of p.P240L in CDH23 in Koreans and its significant contribution to severe-to-profound nonsyndromic hearing loss in a Korean pediatric population

J Transl Med. 2015 Aug 13;13:263. doi: 10.1186/s12967-015-0624-8.


Background: Despite the prevalence of CDH23 mutations in East Asians, its large size hinders investigation. The pathologic mutation p.P240L in CDH23 is common in East Asians. However, whether this mutation represents a common founder or a mutational hot spot is unclear. The prevalence of CDH23 mutations with prelingual severe-to-profound sporadic or autosomal recessive sensorineural hearing loss (arSNHL) is unknown in Koreans.

Methods: From September 2010 to October 2014, children with severe-to-profound sporadic or arSNHL without phenotypic markers, and their families, were tested for mutations in connexins GJB2, GJB6 and GJB3. Sanger sequencing of CDH23 p.P240L was performed on connexin-negative samples without enlarged vestibular aqueducts (EVA), followed by targeted resequencing of 129 deafness genes, including CDH23, unless p.P240L homozygotes were detected in the first screening. Four p.P240L-allele-linked STR markers were genotyped in 40 normal-hearing control subjects, and the p.P240L carriers in the hearing-impaired cohort, to identify the haplotypes.

Results: Four (3.1 %) of 128 children carried two CDH23 mutant alleles, and SLC26A4 and GJB2 accounted for 18.0 and 17.2 %, respectively. All four children showed profound nonsyndromic SNHL with minimal residual hearing. Interestingly, all had at least one p.P240L mutant allele. Analysis of p.P240L-linked STR markers in these children and other postlingual hearing-impaired adults carrying p.P240L revealed that p.P240L was mainly carried on a single haplotype.

Conclusions: p.P240L contributed significantly to Korean pediatric severe arSNHL with a strong founder effect, with implications for future phylogenetic studies. Screening for p.P240L as a first step in GJB2-negative arSNHL Koreans without EVA is recommended.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Asian People / genetics*
  • Cadherin Related Proteins
  • Cadherins / genetics*
  • Child
  • Chromosomes, Human, Pair 10 / genetics
  • Cohort Studies
  • Connexin 26
  • Connexins
  • Deafness / genetics
  • Female
  • Founder Effect*
  • Genetic Predisposition to Disease*
  • Haplotypes / genetics
  • Humans
  • Male
  • Microsatellite Repeats / genetics
  • Mutation / genetics*
  • Pedigree


  • CDH23 protein, human
  • Cadherin Related Proteins
  • Cadherins
  • Connexins
  • GJB2 protein, human
  • Connexin 26

Supplementary concepts

  • Nonsyndromic Deafness