The identification of two mis-sense mutations at the PAH gene locus in a Turkish patient with phenylketonuria.
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.
Konecki
D S
DS
Universitäts-Kinderklinik, Heidelberg, Federal Republic of Germany.
Schlotter
M
M
Trefz
F K
FK
Lichter-Konecki
U
U
D000483:Alleles; D001483:Base Sequence; D002874:Chromosome Mapping; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005971:Glutamates / Q000235:genetics; D018698:Glutamic Acid; D005998:Glycine / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009693:Nucleic Acid Hybridization; D010651:Phenylalanine Hydroxylase / Q000172:deficiency / Q000235:genetics*; D010661:Phenylketonurias / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D014421:Turkey
D005971:Glutamates; D018698:Glutamic Acid; D004247:DNA; D010651:Phenylalanine Hydroxylase; D005998:Glycine