title: WGA allows the molecular characterization of a novel large CFTR rearrangement in a black South African cystic fibrosis patient.
abstract: By performing extensive scanning of whole coding and flanking sequences of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene, we had previously identified the CF-causing mutations in black South African patients of different ethnic groups suspected with the disease. Of ten samples analyzed, there were six remaining that had either one (n = 2) or two (n = 4) unidentified CFTR alleles that have now been tested for large rearrangements using a semiquantitative fluorescent PCR assay. A novel deletion encompassing CFTR exon 2 was detected in one patient who was heterozygous for the mutation 3120+1G>A. The Caucasian deletion involving the same exon [c.54-5811_c.164+2186del8108ins182] was ruled out. The DNA had been stored for more than 12 years and only minute quantities remained. We thus used a whole-genome amplification method based on multiple displacement amplification to generate sufficient amounts of DNA to characterize the intronic breakpoints and identify the deletion at the genomic level. Mapping and sequencing the breakpoint junctions revealed a novel large deletion [c.54-1161_c.164+1603del2875]. We have designed a simple test to specifically detect the presence or absence of this large rearrangement. This study reports the first large CFTR rearrangement in a black South African CF patient, further defining the molecular spectrum of CF that will be useful for improving genetic testing and counseling in this region.
authors.affiliation: INSERM, U827, * Montpellier, F-34000 France.
authors.forename: Marie
authors.initials: M
authors.lastname: des Georges
authors.forename: Caroline
authors.initials: C
authors.lastname: Guittard
authors.forename: Carine
authors.initials: C
authors.lastname: Templin
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Altiéri
authors.forename: Candice
authors.initials: C
authors.lastname: de Carvalho
authors.forename: Michele
authors.initials: M
authors.lastname: Ramsay
authors.forename: Mireille
authors.initials: M
authors.lastname: Claustres
mesh_terms: D001483:Base Sequence; D044383:Black People / Q000235:genetics; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods*; D005091:Exons; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D009154:Mutation; D021141:Nucleic Acid Amplification Techniques; D013019:South Africa; D044465:White People / Q000235:genetics
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator