title: A common founder for the 35delG GJB2 gene mutation in connexin 26 hearing impairment.
abstract: Fifty to eighty percent of autosomal recessive congenital severe to profound hearing impairment result from mutations in a single gene, GJB2, that encodes the protein connexin 26. One mutation of this gene, the 35delG allele, is particularly common in white populations. We report evidence that the high frequency of this allelic variant is the result of a founder effect rather than a mutational hot spot in GJB2, which was the prevailing hypothesis. Patients homozygous for the 35delG mutation and normal hearing controls originating from Belgium, the UK, and the USA were genotyped for different single nucleotide polymorphisms (SNPs). Four SNPs mapped in the immediate vicinity of GJB2, while two were positioned up to 76 kb from it. Significant differences between the genotypes of patients and controls for the five SNPs closest to GJB2 were found, with nearly complete association of one SNP allele with the 35delG mutation. For the most remote SNP, we could not detect any association. We conclude that the 35delG mutation is derived from a common, albeit ancient founder.
authors.affiliation: Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Van Laer
authors.forename: P
authors.initials: P
authors.lastname: Coucke
authors.forename: R F
authors.initials: RF
authors.lastname: Mueller
authors.forename: G
authors.initials: G
authors.lastname: Caethoven
authors.forename: K
authors.initials: K
authors.lastname: Flothmann
authors.forename: S D
authors.initials: SD
authors.lastname: Prasad
authors.forename: G P
authors.initials: GP
authors.lastname: Chamberlin
authors.forename: M
authors.initials: M
authors.lastname: Houseman
authors.forename: G R
authors.initials: GR
authors.lastname: Taylor
authors.forename: C M
authors.initials: CM
authors.lastname: Van de Heyning
authors.forename: E
authors.initials: E
authors.lastname: Fransen
authors.forename: J
authors.initials: J
authors.lastname: Rowland
authors.forename: R A
authors.initials: RA
authors.lastname: Cucci
authors.forename: R J
authors.initials: RJ
authors.lastname: Smith
authors.forename: G
authors.initials: G
authors.lastname: Van Camp
mesh_terms: D000483:Alleles; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D018703:Founder Effect; D005787:Gene Frequency; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26; D004247:DNA