Universitäts-Kinderklinik, Heidelberg, Federal Republic of Germany.
DNA sequence analysis of the 13 exons and intron/exon boundaries of the phenylalanine hydroxylase (PAH) gene has detected two base transitions, resulting in mis-sense mutations, in the genomic DNA of a Turkish patient (E1) with phenylketonuria (PKU). The Leu48----Ser amino acid substitution was associated with the mutant haplotype 3 allele and the Glu221----Gly amino acid substitution with the mutant haplotype 4 allele of this family. Allele-specific oligonucleotide (ASO) dot-blot analysis subsequently detected the Leu48----Ser mutation in the haplotype 4 PKU alleles of nine (18.8%) of the 48 unrelated Caucasian PKU families investigated. This mutation results in mild PKU in the homozygous state. The Glu221----Gly mutation has only been detected within patient E1 and his father.