[Genetic diagnosis of phenylketonuria. IV. Mutations of phenylalanine hydroxylase gene in Caucasian and Gypsy populations in Czech and Slovakia Republics].

[classical phenylketonuria]

Direct sequencing was conducted on the regions of the exon 7 and 12 in the phenylalanine hydroxylase (PAH ) gene amplified by the polymerase chain reaction , using solid-phase technology involving the biotin streptavidin system . A novel mutation and seven previously known mutations were identified in the PAH genes among 15 Caucasians and 10 Gypsies in the Czech and Slovakia republics , affected with classical phenylketonuria (PKU ). Two of these substitutions (R 243 X and G 272 X ) resulted in the generation of a premature stop codon , and a single base transition of G to A at codon 261 resulted in the substitution of Arg for Gln (R 261 Q ). These three mutations together accounted for 16 .7 % of PKU alleles among 15 Caucasians . The R 252 W mutation was detected in these two groups : two Caucasians were compound heterozygous for the P 281 L or R 408 W mutations (6 .7 % of all mutant alleles ). However , all 10 Gypsy PKU patients were homozygous for the R 252 W transition . The R 408 W mutation accounted for 43 % of PKU alleles in 15 Caucasian PKU patients . A novel heterozygous C-to -G transversion at the third base of codon 263 in the exon 7 , resulting in the substitution of Phe for Leu (F 2 63 L ), was detected in a Caucasian PKU patient (3 .3 % of all mutant alleles ). In this study , we revealed a novel PKU mutation of the F 2 63 L in Caucasian populations and a high -risk PKU mutation of the R 252 W in Gypsy populations .