High prevalence of CDH23 mutations in patients with congenital high-frequency sporadic or recessively inherited hearing loss

Orphanet J Rare Dis. 2015 May 13:10:60. doi: 10.1186/s13023-015-0276-z.

Abstract

Background: Mutations in CDH23 are responsible for Usher syndrome 1D and recessive non-syndromic hearing loss. In this study, we revealed the prevalence of CDH23 mutations among patients with specific clinical characteristics.

Methods: After excluding patients with GJB2 mutations and mitochondrial m.1555A > G and m.3243A > G mutations, subjects for CDH23 mutation analysis were selected according to the following criteria: 1) Sporadic or recessively inherited hearing loss 2) bilateral non-syndromic congenital hearing loss, 3) no cochlear malformation, 4) a poorer hearing level at high frequencies than at low frequencies, and 5) severe or profound hearing loss at higher frequencies.

Results: Seventy-two subjects were selected from 621 consecutive probands who did not have environmental causes for their hearing loss. After direct sequencing, 13 of the 72 probands (18.1%) had homozygous or compound heterozygous CDH23 mutations. In total, we identified 16 CDH23 mutations, including five novel mutations. The 16 mutations included 12 missense, two frameshift, and two splice-site mutations.

Conclusions: These results revealed that CDH23 mutations are highly prevalent in patients with congenital high-frequency sporadic or recessively inherited hearing loss and that the mutation spectrum was diverse, indicating that patients with these clinical features merit genetic analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cadherin Related Proteins
  • Cadherins / genetics*
  • Child
  • Child, Preschool
  • Connexin 26
  • Connexins
  • DNA Mutational Analysis
  • Female
  • Hearing Loss / genetics*
  • Hearing Loss, Sensorineural / genetics
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mutation / genetics
  • Phenotype
  • Prevalence
  • Young Adult

Substances

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

Supplementary concepts

  • Deafness, Autosomal Recessive 12