title: Autosomal dominant prelingual hearing loss with palmoplantar keratoderma syndrome: Variability in clinical expression from mutations of R75W and R75Q in the GJB2 gene.
abstract: About one to three of a 1,000 neonates are afflicted at birth with a serious hearing impairment, with about half of the cases due to genetic causes. Genetic causes of hearing impairment are very heterogeneous. About half of all cases of genetically caused nonsyndromic hearing loss can be ascribed to mutations in the GJB2 gene (connexin 26) and to deletions in the GJB6 gene(connexin 30). Thus far, about 90 different mutations have been identified in the GJB2 gene, of which the majority are autosomal recessive. Ten mutations are autosomal dominant and are in most cases associated with various skin diseases: the keratitis-ichthyosis-deafness (KID) syndrome, Vohwinkel syndrome and palmoplantar keratoderma with deafness. To date, the following mutations have been identified which lead to the Palmoplantar Keratoderma syndrome with deafness; Gly59Ala, Gly59Arg, His73Arg, Arg75Trp, and Arg75Gln. We are reporting on four patients with severe hearing impairment. They are members of three unrelated families, who are carriers of mutations Arg75Trp or Arg75Gln, but unlike patients of other publications, do not all present with Palmoplantar Keratoderma syndrome. Our investigations document additional evidence for the correlation between the cited mutations in the GJB2 gene and a syndromic hearing impairment with palmoplantar keratoderma.
authors.affiliation: Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University Medical Center Freiburg, Freiburg, Germany. ralf.birkenhaeger@uniklinik-freiburg.de
authors.forename: Ralf
authors.initials: R
authors.lastname: Birkenhäger
authors.forename: Nicola
authors.initials: N
authors.lastname: Lüblinghoff
authors.forename: Erick
authors.initials: E
authors.lastname: Prera
authors.forename: Christian
authors.initials: C
authors.lastname: Schild
authors.forename: Antje
authors.initials: A
authors.lastname: Aschendorff
authors.forename: Susan
authors.initials: S
authors.lastname: Arndt
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D001483:Base Sequence; D000072259:Connexin 26; D017630:Connexins / Q000737:chemistry / Q000235:genetics*; D004252:DNA Mutational Analysis; D003638:Deafness / Q000150:complications* / Q000235:genetics*; D005190:Family; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D018740:Genetic Heterogeneity; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007645:Keratoderma, Palmoplantar / Q000150:complications* / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011247:Pregnancy; D012867:Skin / Q000473:pathology; D013577:Syndrome
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26