A frequent large rearrangement in the CFTR gene in cystic fibrosis patients from Reunion Island.
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.
Nectoux
Juliette
J
Laboratoire de Biochimie et Génétique Moléculaire, Hôpital Cochin, Paris, France.
Audrezet
Marie Pierre
MP
Viel
Marion
M
Leroy
Chrystel
C
Raguenes
Odile
O
Ferec
Claude
C
Lesure
Jean François
JF
Davy
Nolwenne
N
Renouil
Michel
M
Cartault
François
F
Bienvenu
Thierry
T
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
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator