title: Determination of the carrier frequency of the common GJB2 (connexin-26) 35delG mutation in the Belgian population using an easy and reliable screening method.
abstract: Mutations in the gene GJB2, encoding the gap-junction protein connexin-26, have been shown to be a major cause of nonsyndromic recessive deafness (NSRD). A single mutation in the GJB2 gene accounts for the majority of NSRD in many different populations. This mutation represents a deletion of a guanine within a stretch of six Gs between nucleotide positions +30 and +35 of the GJB2 cDNA (35delG). Molecular detection of the 35delG mutation is usually performed by direct sequencing analysis of PCR products, or by allele-specific PCR analysis. To screen for this mutation, we developed an easier and more reliable method, based on the principle of PCR-mediated site-directed mutagenesis (PSDM), followed by a BsiYI digestion. We tested 360 unrelated unaffected Belgian individuals for heterozygosity of the 35delG mutation and found a carrier frequency of 1 in 40 (95% CI, 1 in 30 to 1 in 60). As our new screening method is simple and reliable in use, and detects a mutation responsible for a significant part of NSRD, it may find widespread use in DNA diagnostics.
authors.affiliation: Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Storm
authors.forename: S
authors.initials: S
authors.lastname: Willocx
authors.forename: K
authors.initials: K
authors.lastname: Flothmann
authors.forename: G
authors.initials: G
authors.lastname: Van Camp
mesh_terms: D001530:Belgium; D001665:Binding Sites / Q000235:genetics; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D017931:DNA Primers; D004262:DNA Restriction Enzymes / Q000378:metabolism; D003638:Deafness / Q000175:diagnosis / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D005808:Genes, Recessive; D006580:Genetic Carrier Screening / Q000379:methods*; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D016133:Polymerase Chain Reaction
chemical_list: D017630:Connexins; D017931:DNA Primers; C000607042:GJB2 protein, human; D000072259:Connexin 26; D004262:DNA Restriction Enzymes