Identification and characterization of three large deletions and a deletion/polymorphism in the CFTR gene

✍ Scribed by F. Chevalier-Porst; G. Souche; D. Bozon

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 73 KB
• Volume: 25
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.9335

✦ Synopsis

Cystic fibrosis (CF) is mainly caused by small molecular lesions of the CFTR gene; mutation detection methods based on conventional PCR do not allow the identification of all CF alleles in a population and large deletions may account for a number of these unidentified molecular lesions. It is only recently that the availability of quantitative PCR methodologies made the search for large gene rearrangements easier in autosomal diseases. Using a combination of different methods, nine of the 37 unidentified CF alleles (24%) were found to harbor large deletions in our cohort of 1600 CF alleles. Three are new deletions, and we report the breakpoints of the previously described EX4_EX10del40kb deletion. An intronic deletion polymorphism affecting intron 17b was also found on almost 1% of "normal" chromosomes. Examination of the breakpoint sequences confirmed that intron 17b is indeed a hot spot for deletions, and that most of these rearrangements are caused by non-homologous recombination.