POPULATION-GENETICS OF HYPERPHENYLALANINEMIA RESULTING FROM PHENYLALANINE-HYDROXYLASE DEFICIENCY IN PORTUGAL

In order to elucidate the molecular basis of phenylketonuria (PKU) in Portugal, a detailed study of the Portuguese mutant phenylalanine hydr oxylase (PAH) genes was performed. A total of 222 mutant alleles from 111 PKU families were analysed for 26 mutations and restriction fragme nt length polymorphism/variable number tandem repeat (RFLP/VNTR) haplo types. It was possible to characterise 55% of the mutant alleles, in w hich 14 different mutations (R261Q, V388M, IVS10nt-11, I65T, P281L, R2 52W, R158Q, L348V, Y414C, L311P, Y198fsdel22bp, R408W, R270K, and R261 X) and three polymorphisms (Q232Q, V245V, and L385L) were identified. A total of 14 different haplotypes were observed, with a high prevalen ce of haplotype 1 among mutant and normal alleles. The results reporte d in this study show considerable genetic heterogeneity in the Portugu ese PKU population, as has also been described for other southern Euro pean populations.