PHENYLKETONURIA IN ITALY - DISTINCT DISTRIBUTION PATTERN OF 3 MUTATIONS OF THE PHENYLALANINE-HYDROXYLASE GENE

Phenylketonuria (PKU) is an autosomal recessive disease caused by the deficiency of a liver-specific enzyme, phenylalanine hydroxylase (PAH) . The pattern of PAH mutations in Mediterranean populations appears to be different from that observed in northern Europe and Asia. Our aim was to study the molecular basis of PKU in Campania and Calabria, two regions of southern Italy. We studied 99 unrelated alleles, detecting 75.8% of the mutations. Our results show that 57% of all the PKU allel es are caused by three different mutations: IVS10nt-546, R261Q and L48 S, which display significant differences in their relative distributio n across Italy. A novel mutation, a G-to-T transversion at the codon 2 57 (G257C), was also identified. This mutation results in a Gly-to-Cys change in the catalytic domain of the protein.