A Phenotype Resembling the Clouston Syndrome with Deafness Is Associated with a Novel Missense GJB2 Mutation

• Published in: Journal of investigative dermatology Vol. 123; no. 2; pp. 291 - 293
• Main Authors: van Steensel, Maurice A.M., Steijlen, Peter M., Bladergroen, Reno S., Hoefsloot, Elisabeth H., van Ravenswaaij-Arts, Connie M., van Geel, Michel
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01.08.2004; Nature Publishing; Elsevier Limited
• Subjects: Amino Acid Sequence; Biological and medical sciences; Child, Preschool; Clouston syndrome; Connexin 26; connexin26; Connexins - genetics; Deafness - genetics; Dermatology; Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology; Ectodermal Dysplasia - genetics; Female; gap junction; GJB2; Hair and nails disorders; Humans; hypotrichosis; Medical sciences; Molecular Sequence Data; Mutation, Missense; Non tumoral diseases; Otorhinolaryngology. Stomatology; Phenotype; GJB2; hypotrichosis; gap junction; Clouston syndrome; connexin26; Human; Hair; Skin disease; Dermatology; Hypotrichosis; Auditory disorder; Hidrotic ectodermal dysplasia; Dermoskeleton; Genetic disease; Hearing loss; Phenotype; Association; Missense mutation; ENT disease; Clouston syndrome/connexin26/gap junction/GJB2/hypotrichosis
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1111/j.0022-202X.2004.23204.x

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.