MUTATION ANALYSIS OF 184 CYSTIC-FIBROSIS FAMILIES IN WALES

We describe a molecular analysis of 184 cystic fibrosis (CF) families in Wales. To determine accurate frequency data for the CF mutations in the Welsh population, families with at least three Welsh grandparents were strictly regarded as Welsh. Of these 74 families, we have identified approximately 90% of mutations causing CF, with DELTA-F508 accounting for 71.8% and 621 + 1G > T 6.7%. We observed a significant difference between the Welsh and Scottish frequencies of 621 + 1 G > T. To allow the rapid and efficient screening for the more common mutations we modified a multiplex used by Watson et al enabling the detection of DELTA-F508, G551D, and R553X simultaneously with 621 + 1G > T. In parallel to this system we ran the Cellmark Diagnostics ARMS multiplex kit, which detects DELTA-F508, 621 + 1G > T, G551D, and G542X. RFLP analysis of the 184 families shows that the DELTA-F508 chromosomes are almost exclusively found on the B haplotype (XV2c 1, KM19 2); the other CF mutations have more heterogeneous backgrounds. Strong haplotype correlations exist between the markers XV2c, KM19, D9, and G2 and the other CF mutations. Haplotype data suggest that there are at least seven mutations that remain to be identified in these families.