Novel mutation p.Gly59Arg in GJB6 encoding connexin 30 underlies palmoplantar keratoderma with pseudoainhum, knuckle pads and hearing loss.
BACKGROUND
Connexins, components of the gap junction, are expressed in several organs including the skin and the cochlea. Mutations in connexin genes including GJB2 (Cx26), GJB3 (Cx31), GJB4 (Cx30.3), GJB6 (Cx30) and GJA1 (Cx43) are responsible for various dermatological syndromes and/or inherited hearing loss, frequently showing overlapping phenotypes.


OBJECTIVE
To clarify the spectrum of clinical phenotypes caused by connexin mutations.


METHODS
We report a 32-year-old Japanese woman with mild palmoplantar keratoderma (PPK) with severe sensorineural hearing loss, knuckle pads and pseudoainhum of her toes.


RESULTS
Direct sequencing revealed no mutation in GJB2, but a novel heterozygous missense mutation p.Gly59Arg in GJB6. Electron microscopy revealed no apparent morphological abnormality of gap junctions in the patient's lesional epidermis.


CONCLUSIONS
The patient harboured the novel GJB6 missense mutation p.Gly59Arg in the first extracellular loop of Cx30. Mutations in glycine 59 of Cx26 are associated with PPK-deafness syndrome, and the similar phenotype here supports the observed heteromeric channel formation; the dominant nature of the mutation suggests an effect on gap junctions similar to that of the comparable mutation in Cx26.
Nemoto-Hasebe
I
I
Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Sapporo, Japan. i-nemoto@med.hokudai.ac.jp
Akiyama
M
M
Kudo
S
S
Ishiko
A
A
Tanaka
A
A
Arita
K
K
Shimizu
H
H
D000328:Adult; D000387:Ainhum / Q000235:genetics*; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005260:Female; D017629:Gap Junctions / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007645:Keratoderma, Palmoplantar / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D010641:Phenotype
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26; C076275:connexin 30.3