FREQUENCIES OF CYSTIC-FIBROSIS MUTATIONS IN THE MAINE POPULATION - HIGH PROPORTION OF UNKNOWN ALLELES IN INDIVIDUALS OF FRENCH-CANADIAN ANCESTRY

Cystic fibrosis (CF) is one of the most common severe autosomal recess ive disorders in Caucasian populations. A mutation in the cystic fibro sis transmembrane conductance regulator (CFTR) gene causes this disord er. Reported here is the first analysis of CF mutations in the Maine p opulation. We have screened 263 CF chromosomes for 16 previously repor ted mutations. Analysis of DNA from 124 apparently unrelated CF patien ts and 15 obligate carrier parents (whose partner and affected child w ere unavailable for study) resulted in the identification of 91% of th e CF alleles and complete genotyping of 85% of the patients. The frequ encies (%) of these mutations in the Maine population are Delta F508 ( 75% of the chromosomes), G85E (0.76), R117H (0.76), I148T (1.1), 621+1 G-->T (1.1), 711+1G-->T (3.0), A455E (1.1), 1717-1G-->A (1.1), G542X ( 1.9), G551D (1.9), R560T (0.76), Y1092X (0.38), W1282X (0.38), and N13 03K (1.5). The exon 10 mutation, Delta I507, and the exon 11 mutation, R553X, were not observed. Surprisingly, whereas only 5% of the allele s remain unidentified in the non-French population, the unidentified p roportion in the French population is 19%. CF testing for the Maine po pulation will be further improved as the as yet unidentified CF mutati ons in this population are characterized.