title: GJB2 mutations in keratitis-ichthyosis-deafness syndrome including its fatal form.
abstract: Keratitis-ichthyosis-deafness syndrome (KID; MIM 148210) is a rare congenital disorder characterized by vascularizing keratitis, sensorineural hearing loss (HL), and progressive erythrokeratoderma. Clinical variability including a fatal course of KID in the first year of life has been reported. Germline missense mutations in GJB2, encoding connexin-26, were recently found to cause KID in 14 unrelated juvenile and adult patients. We identified a de novo GJB2 mutation G45E in a patient displaying the fatal form of the disease. No mutations were detected in five other connexin and mitochondrial genes. The G45E mutation was not reported previously in Caucasian patients but was the third most common GJB2 mutation (16% of disease alleles) in Japanese patients with autosomal recessive non-syndromic HL. This finding suggests different modes of action of the same GJB2 mutation depending on the genetic background. This hypothesis was further substantiated by our observation of a variable clinical course in unrelated KID patients from Austria harboring the common D50N mutation in GJB2.
authors.affiliation: Department of Medical Biology and Human Genetics, Innsbruck Medical University, Schöpfstrasse 41, A-6020 Innsbruck, Austria. Andreas.Janecke@uibk.ac.at
authors.forename: Andreas R
authors.initials: AR
authors.lastname: Janecke
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Hennies
authors.forename: Barbara
authors.initials: B
authors.lastname: Günther
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gansl
authors.forename: Josef
authors.initials: J
authors.lastname: Smolle
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Messmer
authors.forename: Gerd
authors.initials: G
authors.lastname: Utermann
authors.forename: Olaf
authors.initials: O
authors.lastname: Rittinger
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000328:Adult; D002648:Child; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D003638:Deafness / Q000473:pathology*; D017809:Fatal Outcome; D006801:Humans; D007057:Ichthyosis / Q000473:pathology*; D007223:Infant; D007634:Keratitis / Q000473:pathology*; D009154:Mutation; D013577:Syndrome
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26; D004247:DNA