Consequences of partial duplications of the human CFTR gene on cf diagnosis: Mutations or ectopic variations

CFTR exon 10 and its flanking regions are duplicated in the human genome. These duplications present mutations compared to the normal exon 10 sequence. Due to the polymorphic sequence of the 3' intron 9 sequence, it may appear difficult to sequence exon 10 and some mutations described in this exon could, in fact, be variations observed in an ectopic duplicated sequence. In our previous work we described a methodology to carry out PCR only of exon 10 and not of ectopic regions. In this work, we analyzed mutations described in the CF data base as being CFTR mutations but also found in ectopic regions: c.1392G>T, c.1338_1339delAT, c.1235delC, and c.1247A>G. We have shown that these mutations appear to be authentic mutations in CFTR exon 10 and not ectopic variations in analyzed patients. These mutations validate the usefulness of our new strategy in the mutation analysis of this region of CFTR. (c) 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.