title: Evaluation of Cx26/GJB2 in German hearing impaired persons: mutation spectrum and detection of disequilibrium between M34T (c.101T>C) and -493del10.
abstract: Mutations in the connexin 26 gene (GJB2) are responsible for the major part of nonsyndromic autosomal recessive or apparently sporadic prelingual deafness in Caucasians (DFNB1). We screened 228 German hearing-impaired persons for mutations in the GJB2 gene by sequence analysis. Homozygous or compound heterozygous GJB2 mutations were detected in 38/228 (16.7%) of hearing impaired persons. The most frequently occurring mutation was the c.35delG mutation, which was found in 71.1% of the mutated alleles. The next frequent mutation detected in the group of hearing impaired persons was the c.101T>C mutation (9/76 alleles; 11.8%). One new mutation, c.567delA, was observed. We further studied the presence of a 10bp deletion in the 5' UTR of the GJB2 gene (c.-493del10) which was assumed to occur together with the c.101T>C mutation. Ten out of thirteen patients (76.9%) were found to be carriers of both the c.101T>C mutation and the 10bp variant and in 7/14 alleles a linkage disequilibrium between c.101T>C and the 10bp deletion was proven. In 4/14 alleles the linkage was ruled out and for the remaining 3 cases the phase determination was not possible. Seventy one controls were screened for the prevalence of Cx26 mutations and for the c.-493del10 variant. Heterozygosity frequency in the control group was for c.35delG 4.2%, for c.101T>C 1.4% and for c.-493del10 it was 5.6%.
authors.affiliation: Institut für Humangenetik der Universitaet, Goettingen, Germany. bzoll1@gwdg.de
authors.forename: Barbara
authors.initials: B
authors.lastname: Zoll
authors.forename: Lars
authors.initials: L
authors.lastname: Petersen
authors.forename: Katrin
authors.initials: K
authors.lastname: Lange
authors.forename: Peter
authors.initials: P
authors.lastname: Gabriel
authors.forename: Christiane
authors.initials: C
authors.lastname: Kiese-Himmel
authors.forename: Peter
authors.initials: P
authors.lastname: Rausch
authors.forename: Joachim
authors.initials: J
authors.lastname: Berger
authors.forename: Bastian
authors.initials: B
authors.lastname: Pasche
authors.forename: Moritz
authors.initials: M
authors.lastname: Meins
authors.forename: Manfred
authors.initials: M
authors.lastname: Gross
authors.forename: Roswitha
authors.initials: R
authors.lastname: Berger
authors.forename: Eberhard
authors.initials: E
authors.lastname: Kruse
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kunz
authors.forename: Karl
authors.initials: K
authors.lastname: Sperling
authors.forename: Franco
authors.initials: F
authors.lastname: Laccone
mesh_terms: D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D003638:Deafness / Q000175:diagnosis / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D005858:Germany; D006801:Humans; D015810:Linkage Disequilibrium; D019986:Persons with Hearing Disabilities; D010641:Phenotype; D017354:Point Mutation; D017384:Sequence Deletion
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26