title: Bigenic connexin mutations in a patient with hidrotic ectodermal dysplasia.
abstract: Gap junctions are formed by a polygenic family of more than 20 different connexin proteins. They mediate intercellular communication via the direct exchange of ions, metabolites and secondary messengers, thus controlling and coordinating cellular activities. Mutations in five gap junction genes, including GJB2 (Cx26), GJB3 (Cx31), GJB4 (Cx30.3), GJB6 (Cx30) and GJA1 (Cx43) are known to cause inherited hearing loss and/or disorders of the skin and its appendages, often giving rise to overlapping phenotypes. In this study we present a patient with hidrotic ectodermal dysplasia, who had abortive features of oculo-dento-digital dysplasia, extensive hyperkeratosis of the skin. The patient harbored a novel sporadic mutation (V41L) in GJA1 (Cx43) as well as a heterozygous coding variant (R127H) of GJB2 (Cx26). Our findings suggest that GJA1 mutations can produce variable clinical phenotypes on the background of sequence variants in other connexins.
authors.affiliation: Department of Medical Genetics and Child Development, University Medical School of Pécs, József A. u. 7, Pécs 7623, Hungary.
authors.forename: Richard
authors.initials: R
authors.lastname: Kellermayer
authors.forename: Matthew
authors.initials: M
authors.lastname: Keller
authors.forename: Paulina
authors.initials: P
authors.lastname: Ratajczak
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Richardson
authors.forename: Ferenc
authors.initials: F
authors.lastname: Harangi
authors.forename: Eszter
authors.initials: E
authors.lastname: Mérei
authors.forename: Béla
authors.initials: B
authors.lastname: Melegh
authors.forename: György
authors.initials: G
authors.lastname: Kosztolányi
authors.forename: Gabriele
authors.initials: G
authors.lastname: Richard
mesh_terms: D002648:Child; D000072259:Connexin 26; D018031:Connexin 43 / Q000235:genetics*; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004476:Ectodermal Dysplasia / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction; D006178:Romani People
chemical_list: D018031:Connexin 43; D017630:Connexins; C500216:GJA1 protein, human; C000607042:GJB2 protein, human; D000072259:Connexin 26