title: A phenotype resembling the Clouston syndrome with deafness is associated with a novel missense GJB2 mutation.
abstract: 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.
authors.affiliation: Department of Dermatology, University Medical Centre Nijmegen, The Netherlands. mvst@sder.azm.nl
authors.forename: Maurice A M
authors.initials: MA
authors.lastname: van Steensel
authors.forename: Peter M
authors.initials: PM
authors.lastname: Steijlen
authors.forename: Reno S
authors.initials: RS
authors.lastname: Bladergroen
authors.forename: Elisabeth H
authors.initials: EH
authors.lastname: Hoefsloot
authors.forename: Connie M
authors.initials: CM
authors.lastname: van Ravenswaaij-Arts
authors.forename: Michel
authors.initials: M
authors.lastname: van Geel
mesh_terms: 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
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26