Genetic heterogeneity in five Italian regions: Analysis of PAH mutations and minihaplotypes

Molecular analysis of 289 chromosomes has been performed in a cohort of phe nylketonuria (PKU) patients whose ancestors lived in five Italian regions, Calabria, Campania, Piemonte, Puglia/Basilicata and Sicilia. Phenylalanineh ydroxylase (PAH) gene mutations and minihaplotypes (combinations of PAH gen e STR and VNTR systems) have been determined for 78.5 and 64%, respectively , of the chromosomes studied. 21 different minihaplotypes and 24 PKU mutati ons were found. Heterogeneity tests carried out for the frequencies of muta tions and minihaplotypes show that the distribution of eight mutations and four minihaplotypes is statistically heterogeneous in the five Italian regi ons. Although the evolutionary rate of microsatellites or the age of these mutations is difficult to estimate with accuracy, our findings taken togeth er show a genetic stratification of the Italian population. These results r ule out allelic homogeneity of PKU at the molecular level between regions o f Italy, yet minihaplotype data may be of practical use for a multistep app roach to PAH gene genotyping. Copyright (C) 2001 S. Karger AG, Basel.