2 NOVEL PAH GENE-MUTATIONS DETECTED IN ITALIAN PHENYLKETONURIC PATIENTS

We report the identification by denaturing gradient gel electrophoresi s and sequence analysis of two new phenylalanine hydroxylase (PAH) gen e mutations (IVS4nt-2 and N207S) in single chromosomes of two unrelate d Italian phenylketonuric (PKU) patients. Interestingly, mutation Y204 C, found on the second mutant allele of family F1, has been previously detected in Chinese patients. Haplotype analysis showed that the latt er mutation is linked to the same haplotype (H4) in both Chinese and I talian patients, suggesting a common origin. In vivo assessment of mut ation severity indicates that N207S is associated with classic PKU. Th e identification of these two new mutations further extends the remark able heterogeneity of the PAH locus in the Italian population.