INFORMATIVITY OF INTRAGENIC MICROSATELLITES FOR CARRIER DETECTION ANDPRENATAL-DIAGNOSIS OF CYSTIC-FIBROSIS IN THE ITALIAN POPULATION

Molecular diagnosis of cystic fibrosis (CF) in the Italian population, based on the detection of the deltaF508 mutation (51.2% of CF chromos omes), provides full informativity for prenatal diagnosis (PDN) in abo ut 28% of families at risk. Identification of the predominant non-delt aF508 mutations allows the characterization of about 70% of CF chromos omes, making approximately 48% of couples fully informative. In famili es where at least one chromosome remains uncharacterized, allele segre gation is still determined using RFLPs closely linked to the CF gene. The recent identification of three polymorphic clusters of dinucleotid e repeats (IVS8/ GT, IVS17b/TA and IVS17b/CA) led us to evaluate wheth er their analysis might improve feasibility studies for prenatal diagn osis or heterozygote identification. One hundred nuclear families with a CF child, reflecting the general Italian deltaF508 mutation distrib ution, were genotyped for the three microsatellites. In this study mic rosatellite analysis using IVS8/GT and IVS17b/TA allowed the identific ation of both parental CF chromosomes in 94% of couples; inclusion in the study of the less polymorphic repeat locus, IVS17b/CA, slightly im proved this percentage (97%). Hence, a strategy involving primarily th e detection of the deltaF508 mutation and secondarily microsatellite a nalysis makes possible PDN of CF in virtually all Italian CF families.