4 NOVEL CYSTIC-FIBROSIS MUTATIONS IN SPLICE JUNCTION SEQUENCES AFFECTING THE CFTR-NUCLEOTIDE BINDING FOLDS

Single cases of the four novel splice site mutations 1526-1 G → A (intron 9), 3601-2 A → G (intron 18), 3850-3 T → G (intron 19), and 4374<1 G → T (intron 23) were detected in the CFTR gene of cystic fibrosis patients of Indo-Iranian, Turkish, Polish, and German descent. The nucleotide substitutions at the <1, -1, and -2 positions all destroy splice sites and lead to severe disease alleles associated with features typical of gastrointestinal and pulmonary cystic fibrosis disease. The 3850-3 T-to-G change was discovered in a very mildly affected 33-year-old ΔF508 compound heterozygoteJ suggesting that the T-to-G transversion at the less conserved -3 position of the acceptor splice site may retain some wildtype function. © 1993 Academic Press, Inc.