MOLECULAR-GENETIC ANALYSIS OF SOME MUTATI ONS IN THE CYSTIC-FIBROSIS GENE IN MOLDOVA - CHARACTERIZATION OF MOLECULAR MARKERS AND THEIR LINKAGE TO VARIOUS MUTATIONS

Sixty-one patients with cystic fibrosis (CF) from Moldova were tested for mutations DELTAF508, G551D, and R553X. Frequencies of various alle les of the repeated GATT sequence in intron 6B of the CFTR gene, their linkage to other polymorphic markers, and various mutations were dete rmined. The frequency of occurrence of mutation DELTAF508 was only 25% . An absolute majority of CF patients (80%) had pancreatic insufficien cy. Mutations G551D and R553X were not found in our sample. Each of 31 chromosomes with mutation DELTAF508 carries the 6-GATT allele. Most ' 'non DELTAF508'' (78%) and normal (80%) chromosomes were marked by 7-G ATT allele. Twenty-seven DELTAF508 chromosomes (96.4%) belong to haplo type B6, and only one to D6. Most chromosomes with ''non DELTAF508'' m utations are associated with haplotypes D7 (26.3%) and C7 (21%). In ad dition, a significant portion of chromosomes from this subgroup were a ssociated with haplotypes A7 (23.7%), A6 (10.5%), and C6 (2.7%), which are not yet described for mutant chromosomes. The results obtained de monstrate that CF in Moldova is mainly associated with mutations other than DELTAF508, G551D, and R553X. Severe forms of the disease, with p ancreatic insufficiency, are more frequently caused by these mutations ; moreover, our data provides strong evidence about the presence of at least seven additional CF mutations in Moldova, apart from DELTAF508, G551D, and R553X. Some of these are probably not described.