Human Molecular Genetics, 2000, Vol. 9, No. 1 63-67
© 2000 Oxford University Press
Mutations in connexin31 underlie recessive as well as dominant non-syndromic hearing loss
1Department of Human Genetics and 2Department of Otolaryngology, Medical College of Virginia of Virginia Commonwealth University, Richmond, VA 23298-0033, USA, 3Department of Otolaryngology, West China University of Medical Sciences, Chengdu 610041, China, 4Department of Pediatrics, University of Virginia, Charlottesville, VA 22908, USA, 5MRC Mammalian Genetics Unit and UK Mouse Genome Center, Harwell, Oxon OX11 ORD, UK and 6MRC Institute of Hearing Research, University Park, Nottingham NG7 2RD, UK
Mutations in the GJB3 gene encoding connexin31 (Cx31) can cause a dominant non-syndromic form of hearing loss (DFNA2). To determine whether mutations at this locus can also cause recessive non-syndromic deafness, we screened 25 Chinese families with recessive deafness and identified in two families affected individuals who were compound heterozygotes for Cx31 mutations. The three affected individuals in the two families were born to non-consanguineous parents and had an early onset bilateral sensorineural hearing loss. In both families, differing SSCP patterns were observed in affected and unaffected individuals. Sequence analysis in both families demonstrated an in-frame 3 bp deletion (423–425delATT) in one allele, which leads to the loss of an isoleucine residue at codon 141, and a 423A
G transversion in the other allele, which creates an IleVal substitution at codon 141 (I141V). Neither of these two mutations was detected in DNA from 100 unrelated control subjects. The altered isoleucine residue lies within the third conserved 
-helical transmembrane domain (M3), which is critical for the formation of the wall of the gap junction pore. Both the deletion of the isoleucine residue 141 and its substitution to valine in the two families could alter the structure of M3, and impair the function of the gap junction. The present data demonstrate that, like mutations in connexin26, mutations in Cx31 can lead to both recessive and dominant forms of non-syndromic deafness.
+ To whom correspondence should be addressed at: Department of Human Genetics, Medical College of Virginia of Virginia Commonwealth University, Sanger Hall, 1101 East Marshall Street, Richmond, VA 23298-0033, USA. Tel: +1 804 828 9632; Fax: +1 804 828 3760; Email: xzliu@hsc.vcu.edu
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