A new, recurrent mutation of GJB3 (Cx31) in erythrokeratodermia variabilis

Abstract

This mutation is the first to affect a conserved residue in the cytoplasmic carboxy-terminus of any connexin gene with a cutaneous phenotype, emphasizing its structural and/or functional importance.

Erythrokeratoderma variabilis caused by a recessive mutation in GJB3

“…The mutation spectrum in GJB3 includes eight distinct missense mutations causing EKV, 11 several missense mutations and two small deletions leading to sensorineural deafness, 12–16 and one small deletion that results in sensorineural deafness and peripheral neuropathy 17 . The clinical phenotype associated with GJB3 mutations seems to be largely determined by the location of the amino acid substitution and the specific domain affected by the mutation 4 .…”

A sporadic elder case of erythrokeratodermia variabilis with a single base‐pair transversion in GJB3 gene successfully treated with systemic vitamin A derivative

“…The disease-causing mutation (c.625C>T; p.L209F) has been reported previously in two patients (a 14-year-old boy from Australia and a 22-year-old woman from Scotland) with EKV. 4 The boy was a sporadic and de novo case. The two patients manifested EKV soon after birth and developed slowly progressive, relatively stable hyperkeratotic plaques in a symmetrical distribution.…”

Gap Junctions in Development and Disease

“…All mutations result in replacement of amino acid residues highly conserved among β-connexins and are predicted to exert a dominant negative effect on the function of co-expressed wild-type connexins. With the exception of one recurrent mutation that lies in the cytoplasmic carboxy-terminal tail of Cx31 (L209F; Morley et al 2005, Feldmeyer et al 2005, all other mutations cluster either in the cytoplasmic aminoterminus (G12D, G12R) or the membrane-crossing α-helices of Cx31 (R42P, C86S, F137L) and Cx30.3 (R22H, T85P, F137L, F189L;Fig. 7.4;Richard et al 1998aRichard et al , 2003Wilgoss et al 1999;Macari et al 2000).…”