Molecular basis of childhood deafness resulting from mutations in the GJB2(connexin 26) gene

Mutations in the GJB2 gene have been identified in many patients with child hood deafness, 35delG being the most common mutation in Caucasoid populatio ns. We have analyzed a total of 576 families/unrelated patients with recess ive or sporadic deafness from Italy and Spain, 193 of them brine referred a s autosomal recessive, and the other 383 as apparently sporadic cases (sing letons). Of the 1152 unrelated GJB2 chromosomes analyzed from these patient s, 37% had GJB2 mutations. Twenty three different mutations were detected ( 1 in-frame deletion, 4 nonsense, 5 frameshift, and 13 missense mutations). Mutation 35delG was the most comment accounting for 82% of all GJB2 deafnes s alleles. The relative frequency of 35delG in Italy and Spain was differen t, representing 88% of the alleles in Italian patients and only 55% in the Spanish cases. Eight non-35delG mutations were detected more than once (V37 I, E47X, 167delT, L90P, 312del14, 334delAA, R143W, and R184P), with relativ e frequencies ranging between 0.5 and 1.6% of the GJB2 deafness alleles. Th e information based on conservation of amino acid residues, coexistence wit h a second GJB2 mutation or absence of the mutation in non-deaf control sub jects, suggests that most of these missense changes should be responsible f or the deafness phenotype.