A phenotype resembling the Clouston syndrome with deafness is associated with a novel missense GJB2 mutation.
Mutations in GJB2 (connexin26) are associated with skin disorders and deafness. The Clouston syndrome (MIM129500) is associated with mutations in GJB6 (connexin30). Here, we describe a patient suffering from a Clouston-syndrome-like phenotype of thin hair, deafness, nail dystrophy, and mild erythrokeratoderma, caused by a novel spontaneous missense mutation in GJB2. The heterozygous mutation in codon 42, AAC>AAG, changes asparagine to lysine (N14K). Interestingly, this asparagine is near two of the residues mutated in Keratitis-like ichthyosis deafness (KID) syndrome (G12R and S17F), yet the phenotype associated with N14K strongly differs from the KID phenotype. Instead, there is a clear phenotypic overlap with syndromes associated with connexin26 or 30 mutations. Our finding suggest that careful audiological evaluation of patients suffering from Clouston-syndrome-like phenotypes is warranted and expand the spectrum of connexin26-associated disease.
van Steensel
Maurice A M
MA
Department of Dermatology, University Medical Centre Nijmegen, The Netherlands. mvst@sder.azm.nl
Steijlen
Peter M
PM
Bladergroen
Reno S
RS
Hoefsloot
Elisabeth H
EH
van Ravenswaaij-Arts
Connie M
CM
van Geel
Michel
M
D000595:Amino Acid Sequence; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D004476:Ectodermal Dysplasia / Q000235:genetics*; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010641:Phenotype
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26