Prevalence and clinical features of hearing loss patients with CDH23 mutations: a large cohort study

PLoS One. 2012;7(8):e40366. doi: 10.1371/journal.pone.0040366. Epub 2012 Aug 10.

Abstract

Screening for gene mutations in CDH23, which has many exons, has lagged even though it is likely to be an important cause for hearing loss patients. To assess the importance of CDH23 mutations in non-syndromic hearing loss, two-step screening was applied and clinical characteristics of the patients with CDH23 mutations were examined in this study. As a first screening, we performed Sanger sequencing using 304 probands compatible with recessive inheritance to find the pathologic mutations. Twenty-six possible mutations were detected to be pathologic in the first screening. For the second screening, using the probes for these 26 mutations, a large cohort of probands (n = 1396) was screened using Taqman amplification-based mutation analysis followed by Sanger sequencing. The hearing loss in a total of 52 families (10 homozygous, 13 compound heterogygous, and 29 heterozygous) was found to be caused by the CDH23 mutations. The majority of the patients showed congenital, high frequency involved, progressive hearing loss. Interestingly, some particular mutations cause late onset moderate hearing loss. The present study is the first to demonstrate the prevalence of CDH23 mutations among non-syndromic hearing loss patients and indicated that mutations of the CDH23 gene are an important cause of non-syndromic hearing loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Cadherin Related Proteins
  • Cadherins / genetics*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Consanguinity
  • Exons
  • Female
  • Gene Frequency
  • Genes, Recessive
  • Genotype
  • Hearing Loss / diagnosis
  • Hearing Loss / epidemiology*
  • Hearing Loss / genetics*
  • Hearing Tests
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Mutation*
  • Pedigree
  • Phenotype
  • Prevalence
  • Young Adult

Substances

  • CDH23 protein, human
  • Cadherin Related Proteins
  • Cadherins

Grants and funding

This study was supported by a Health and Labour Sciences Research Grant for Comprehensive Research on Disability Health and Welfare from the Ministry of Health, Labour and Welfare of Japan (http://www.mhlw.go.jp/english/) (SU), by the Acute Profound Deafness Research Committee of the Ministry of Health, Labour and Welfare of Japan (http://www.mhlw.go.jp/english/) (SU), by a Health and Labour Sciences Research Grant for Research on Specific Diseases (Vestibular Disorders) from the Japanese Ministry of Health, Labour and Welfare (http://www.mhlw.go.jp/english/) (SU), and by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (http://www.mext.go.jp/english/) (SU). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.