Identification of a novel mutation R42P in the gap junction protein beta-3associated with autosomal dominant erythrokeratoderma variabilis

We report a missense mutation in the gap junction protein beta-3 (encoding Connexin 31), which was detected in only the affected members of a family i n which the autosomal dominant skin disease erythrokeratoderma variabilis w as segregating. The nucleotide change results in an arginine to proline sub stitution in codon 42. This residue is positioned on the first transmembran e/first extracellular domain of the gap junction protein with the mutation replacing a negatively charged residue with a nonpolar residue. This change may disrupt the conformation of the protein and voltage gating polarity le ading to impaired channel function.