A novelGJB6missense mutation in hidrotic ectodermal dysplasia 2 (Clouston syndrome) broadens its genotypic basis

Conflicts of interest: none declared. Hidrotic ectodermal dysplasia 2 (HED2), also known as Clouston syndrome (OMIM #129500), is a rare autosomal dominant skin disorder characterized by generalized hypotrichosis with alopecia, nail dystrophy, palmoplantar hyperkeratosis, normal sweating and normal dentition.1 Positional cloning identified GJB6 on chromosome 13q12 as the causative gene for Clouston syndrome.1,GJB6 encodes connexin 30 (Cx30), which belongs to a family of cell membrane proteins, the connexins, which form gap junctions between neighbouring cells. Like all connexins, GJB6 has four transmembrane domains linked by two extracellular loops and a cytoplasmic loop, along with a cytoplasmic amino‐terminus and a cytoplasmic carboxy‐terminus tails. In addition to HED2, mutations in Cx30 have been identified in autosomal dominant (DFNA3) and autosomal recessive (DFNB1) nonsyndromic sensorineural hearing loss, and in at least one case of the keratitis‐ichthyosis‐deafness (KID) syndrome. To date, all patients with HED2 have been found to have one of three GJB6 missense mutations, G11R, V37E or A88V, all of which lead to nonsynonymous amino acid substitutions.1 2–3