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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2015

Open Access 01-12-2015 | Research

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

Authors: So Young Kim, Ah Reum Kim, Nayoung K D Kim, Min Young Kim, Eun-Hee Jeon, Bong Jik Kim, Young Eun Han, Mun Young Chang, Woong-Yang Park, Byung Yoon Choi

Published in: Journal of Translational Medicine | Issue 1/2015

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Abstract

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.
Appendix
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Metadata
Title
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
Authors
So Young Kim
Ah Reum Kim
Nayoung K D Kim
Min Young Kim
Eun-Hee Jeon
Bong Jik Kim
Young Eun Han
Mun Young Chang
Woong-Yang Park
Byung Yoon Choi
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2015
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-015-0624-8

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