title: A frequent large rearrangement in the CFTR gene in cystic fibrosis patients from Reunion Island.
abstract: Reunion Island is a French province, 800 km east of Madagascar and 200 km west of Mauritius. On Reunion Island, the birth prevalence of cystic fibrosis (CF) is particularly high in the population of European origin, approximately 1:1000. In a previous study, we demonstrated that the screening of the 27 exons of the CF transmembrane conductance regulator (CFTR) gene by denaturing high-pressure liquid chromatography (DHPLC) in 114 CF families allowed the detection of about 93% of the molecular defects present on Reunion Island. Unidentified CF mutations may lie in introns or in regulatory regions that are not routinely investigated, or may correspond to gene rearrangements such as large, heterozygous deletions that escape detection using current PCR-based techniques. Using a combination of different methods (such as multiplex ligation-dependent probe amplification), 6 of the 13 unidentified CF alleles (46%) were found to harbor a deletion of 5288 bp, spanning from exon 17a to 18. Identification and examination of the breakpoint sequences showed that this deletion is different from the 3120+1kbdel8.6Kb previously found in the Palestinian Arabs. The chromosomes bearing IVS16+3316_IVS18+644del5288 did not have a common extragenic haplotype. Clinical evaluation of homozygotes (2 unrelated patients) and compound heterozygotes indicated that this deletion represents a severe mutation associated with positive sweat chloride test, pancreatic insufficiency, and early age at diagnosis.
authors.affiliation: Laboratoire de Biochimie et Génétique Moléculaire, Hôpital Cochin, Paris, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Nectoux
authors.forename: Marie Pierre
authors.initials: MP
authors.lastname: Audrezet
authors.forename: Marion
authors.initials: M
authors.lastname: Viel
authors.forename: Chrystel
authors.initials: C
authors.lastname: Leroy
authors.forename: Odile
authors.initials: O
authors.lastname: Raguenes
authors.forename: Claude
authors.initials: C
authors.lastname: Ferec
authors.forename: Jean François
authors.initials: JF
authors.lastname: Lesure
authors.forename: Nolwenne
authors.initials: N
authors.lastname: Davy
authors.forename: Michel
authors.initials: M
authors.lastname: Renouil
authors.forename: François
authors.initials: F
authors.lastname: Cartault
authors.forename: Thierry
authors.initials: T
authors.lastname: Bienvenu
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000369:Aged, 80 and over; D001483:Base Sequence; D002648:Child; D019457:Chromosome Breakage; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D010375:Pedigree; D011995:Recombination, Genetic; D017508:Reunion; D017384:Sequence Deletion
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator