CHARACTERIZATION OF PHENYLKETONURIA ALLELES IN THE ITALIAN POPULATION

In order to identify the molecular basis of phenylketonuria (PKU) in I taly, we screened the entire coding sequence of the phenylalanine hydr oxylase gene in 20 Italian PKU patients, whose origins are scattered t hroughout Italy. The frequency of each identified mutation and of 5 ot her European mutations was determined within a panel of 92 Italian PKU patients. This approach allowed us to identify 20 different PKU mutat ions and characterize 64% of the Italian PKU chromosomes. Eleven mutat ions (IVS10nt546, L48S, R158Q, R261Q, P281L, R261X, R252W, Delta T55, IVS7nt1, IVS12nt1, Y414C) represent 55.4% of the Italian PKU alleles, the most common mutations being IVS10nt546 (12.4%) and L48S (9%). All the other mutations are very rare. These data confirm the great hetero geneity expected from previous RFLP haplotype studies. Genotype/phenot ype correlation allowed for assessment of the clinical impact of the 2 0 identified mutations.