Human Molecular Genetics, 2001, Vol. 10, No. 25 2945-2951
© 2001 Oxford University Press
Mutations in GJA1 (connexin 43) are associated with non-syndromic autosomal recessive deafness
1Department of Human Genetics, Medical College of Virginia of Virginia Commonwealth University, Richmond, VA 23298-0033, USA, 2Department of Otolaryngology, University of Miami, Miami, FL 33101, USA, 3Department of Otolaryngology, Harvard Medical School and Massachusetts Eye and Ear Infirmary and 4Neurology Department, Massachusetts General Hospital and Neurobiology Department, Harvard Medical School, Boston, MA 02114, USA and 5Department of Biology, Gallaudet University, 800 Florida Avenue NE, Washington, DC 20002, USA
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 ValAla 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 
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.
+ To whom correspondence should be addressed at: Department of Otolaryngology (D-48), University of Miami, 1666 NW 12th Avenue, Miami, FL 33136, USA. Tel: +1 305 243 4923; Fax: +1 305 243 4925; Email: xliu@med.miami.edu
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