title: Detection of 98.5% of the mutations in 200 Belgian cystic fibrosis alleles by reverse dot-blot and sequencing of the complete coding region and exon/intron junctions of the CFTR gene.
abstract: We have previously shown that about 85% of the mutations in 194 Belgian cystic fibrosis alleles could be detected by a reverse dot-blot assay. In the present study, 50 Belgian chromosomes were analyzed for mutations in the cystic fibrosis transmembrane conductance regulator gene by means of direct solid phase automatic sequencing of PCR products of individual exons. Twenty-six disease mutations and 14 polymorphisms were found. Twelve of these mutations and 3 polymorphisms were not described before. With the exception of one mutant allele carrying two mutations, these mutations were the only mutations found in the complete coding region and their exon/intron boundaries. The total sensitivity of mutant CF alleles that could be identified was 98.5%. Given the heterogeneity of these mutations, most of them very rare, CFTR mutation screening still remains rather complex in our population, and population screening, whether desirable or not, does not appear to be technically feasible with the methods currently available.
authors.affiliation: Center for Human Genetics, University of Leuven, Belgium.
authors.forename: H
authors.initials: H
authors.lastname: Cuppens
authors.forename: P
authors.initials: P
authors.lastname: Marynen
authors.forename: C
authors.initials: C
authors.lastname: De Boeck
authors.forename: J J
authors.initials: JJ
authors.lastname: Cassiman
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D001530:Belgium; D018118:Chloride Channels / Q000235:genetics; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005091:Exons; D016368:Frameshift Mutation; D006801:Humans; D007438:Introns; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D017354:Point Mutation; D011110:Polymorphism, Genetic; D017384:Sequence Deletion
chemical_list: C505032:CFTR protein, human; D018118:Chloride Channels; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator