IDENTIFICATION OF MUTATIONS IN THE CONNEXIN-26 GENE THAT CAUSE AUTOSOMAL RECESSIVE NONSYNDROMIC HEARING-LOSS

Mutations in the Cx26 gene have been shown to cause autosomal recessiv e nonsyndromic hearing loss (ARNSHL) at the DFNB1 locus on chromosome 13q12, Using direct sequencing, we screened the Cx26 coding region of affected and nonaffected members from seven ARNSHL families either lin ked to the DFNB1 locus or in which the ARNSHL phenotype cosegregated w ith markers from chromo some 13q12, Cx26 mutations were found in six o f the seven families and included two previously described mutations ( W24X and W77X) and two novel Cx26 mutations: a single base pair deleti on of nucleotide 35 resulting in a frameshift and a C-to-T substitutio n at nucleotide 370 resulting in a premature stop codon (Q124X). We ha ve developed and optimized allele-specific PCR primers for each of the four mutations to rapidly determine carrier and noncarrier status wit hin families, We also have developed a single stranded conformational polymorphism (SSCP) assay which covers the entire Cx26 coding region, This assay can be used to screen individuals with nonsyndromic hearing loss for mutations in the CX26 gene. (C) 1998 Wiley-Liss, Inc.