title: Molecular genetics of PKU in eastern Europe: a nonsense mutation associated with haplotype 4 of the phenylalanine hydroxylase gene.
abstract: Phenylketonuria (PKU) is a genetic disorder secondary to a deficiency of hepatic phenylalanine hydroxylase (PAH). Several mutations in the PAH gene have recently been reported, and linkage disequilibrium was observed between RFLP haplotypes and specific mutations. A new molecular lesion has been identified in exon 7 of the PAH gene in a Hungarian PKU patient by direct sequencing of PCR-amplified DNA. The C-to-T transition causes the substitution of Arg243 to a termination codon, and the mutant allele is associated with haplotype 4 of the PAH gene. The mutation is present in two of nine mutant haplotype 4 alleles among Eastern Europeans and is not present among Western Europeans and Asians. The rarity of this mutant allele and its restricted geographic distribution suggest that the mutational event occurred recently on a normal haplotype 4 background in Eastern Europe.
authors.affiliation: Howard Hughes Medical Institute, Department of Cell Biology, Houston, Texas.
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Okano
authors.forename: R C
authors.initials: RC
authors.lastname: Eisensmith
authors.forename: G
authors.initials: G
authors.lastname: Fekete
authors.forename: D
authors.initials: D
authors.lastname: Schuler
authors.forename: G
authors.initials: G
authors.lastname: Berencsi
authors.forename: I
authors.initials: I
authors.lastname: Nasz
authors.forename: S L
authors.initials: SL
authors.lastname: Woo
mesh_terms: D000483:Alleles; D001483:Base Sequence; D005061:Europe, Eastern; D005091:Exons / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D009154:Mutation; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D010375:Pedigree; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000235:genetics*; D016133:Polymerase Chain Reaction
chemical_list: D015345:Oligonucleotide Probes; D010651:Phenylalanine Hydroxylase