MUTATION ANALYSIS AND HAPLOTYPE CORRELATION FOR 139 CYSTIC-FIBROSIS PATIENTS FROM THE NEBRASKA REGIONAL CYSTIC-FIBROSIS CENTER

Cystic fibrosis (CF) is the most common autosomal recessive disorder i n Caucasian populations with an approximate frequency of one in 2,500 live births and a carrier frequency of one in 25. We studied 400 indiv iduals seen at The Nebraska Regional Cystic Fibrosis Center that inclu ded 139 CF patients, 206 parents, and 55 unaffected siblings to determ ine the frequency of the DELTAF508, R117H, G542X, S549R/N, G551D, R553 X, R560T, and W1282X mutations. In addition, we determined haplotypes on each of these individual's chromosomes using four markers that incl uded XV-2c, KM-19, pMP6d.9, and G2. Results from this study showed tha t the DELTAF508 mutation was present in 70% of CF chromosomes. Of the 139 CF patients 74 (53%) were homozygous for the DELTAF508 deletion, 4 7 (34%) were heterozygous for the DELTAF508 deletion and an unknown mu tation, and 18 (13%) carried two unknown mutations. Four additional mu tations were also found in our population and included G542X (6%), G55 1D (5%), R553X (4%), and R560T (1%). One patient was documented to be a compound heterozygote for G542X/G551D. A polymorphism, F508C, that h as previously been reported in several families was also present in ou r study. The most common haplotype associated with the DELTAF508 delet ion in our CF patients was the E haplotype (CF Consortium B) while oth er mutations were associated with a variety of haplotypes.