Mutations in GJA1 (Connexin 43) Are Associated With Non-Syndromic Autosomal Recessive Deafness

Hum Mol Genet. 2001 Dec 1;10(25):2945-51. doi: 10.1093/hmg/10.25.2945.

Abstract

Mutations in four members of the connexin gene family have been shown to underlie distinct genetic forms of deafness, including GJB2 [connexin 26 (Cx26)], GJB3 (Cx31), GJB6 (Cx30) and GJB1 (Cx32). We have found that alterations in a fifth member of this family, GJA1 (Cx43), appear to cause a common form of deafness in African Americans. We identified two different GJA1 mutations in four of 26 African American probands. Three were homozygous for a Leu-->Phe substitution in the absolutely conserved codon 11, whereas the other was homozygous for a Val-->Ala transversion at the highly conserved codon 24. Neither mutation was detected in DNA from 100 control subjects without deafness. Cx43 is expressed in the cochlea, as is demonstrated by PCR amplification from human fetal cochlear cDNA and by RT-PCR of mouse cochlear tissues. Immunohistochemical staining of mouse cochlear preparations showed immunostaining for Cx43 in non-sensory epithelial cells and in fibrocytes of the spiral ligament and the spiral limbus. To our knowledge this is the first alpha connexin gene to be associated with non-syndromic deafness. Cx43 must also play a critical role in the physiology of hearing, presumably by participating in the recycling of potassium to the cochlear endolymph.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cochlea / metabolism*
  • Connexin 43 / genetics*
  • Connexin 43 / metabolism
  • Connexins
  • DNA Mutational Analysis
  • DNA Primers / chemistry
  • Deafness / genetics*
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Mice
  • Mice, Inbred CBA
  • Molecular Sequence Data
  • Mutation / genetics*
  • Pedigree
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Syndrome

Substances

  • Connexin 43
  • Connexins
  • DFNA3 protein, human
  • DNA Primers

Associated data

  • RefSeq/XM_027459