P67L - A CYSTIC-FIBROSIS ALLELE WITH MILD EFFECTS FOUND AT HIGH-FREQUENCY IN THE SCOTTISH POPULATION

Only three mutant cystic fibrosis (CF) alleles have to date been estab lished as conferring a dominant mild effect on affected subjects who a re compound heterozygotes. We now add a fourth, P67L, which occurs on about 1.4% of Scottish CF chromosomes. Among 13 patients (12 unrelated ) with this allele, the average age at diagnosis was 22.5+/-11.3 years . None of the cases had consistently raised sweat chloride concentrati ons, the average value being 57+/-9 mmol/l; 77% of the patients were p ancreatic sufficient. When compared to three other established mild CF alleles, R117H, A455E, and 3849+10kb C-T, a compound heterozygote for P67L has minimal disease and clinical suspicions are unlikely to be c onfirmed other than by DNA typing.