title: Phenylketonuria in the Greek population. Haplotype analysis of the phenylalanine hydroxylase gene and identification of a PKU mutation.
abstract: Haplotype analysis of the phenylalanine hydroxylase (PAH) gene was performed on 27 chromosomes from a sample of 14 Greek phenylketonuria (PKU) probands and their parents. The majority (94%) of the 17 mutant PAH alleles are on haplotypes 1, 2 and 4, with haplotype 1 being most common. Sixty per cent of ten control PAH alleles are on haplotypes 1, 2 and 4. Haplotype 3 was not present in either group. A new MspI restriction site was found in exon 9 of a single mutant PAH allele on haplotype 7. The mutation responsible for the restriction site alteration is a T to C transition at nucleotide 1154 of the PAH cDNA, resulting in the conversion of codon 311 from leucine to proline (L311P). The same mutation has been described on a haplotype 1 allele in a German PKU patient. A single crossover event would be required to transfer this mutation from haplotype 1 to 7. Migration of this mutation from one haplotype to another by recombination cannot be distinguished from a recurrent mutation at this site.
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: K J
authors.initials: KJ
authors.lastname: Hofman
authors.forename: S E
authors.initials: SE
authors.lastname: Antonarakis
authors.forename: S
authors.initials: S
authors.lastname: Missiou-Tsangaraki
authors.forename: C D
authors.initials: CD
authors.lastname: Boehm
authors.forename: D
authors.initials: D
authors.lastname: Valle
mesh_terms: D000483:Alleles; D001483:Base Sequence; D015139:Blotting, Southern; D004247:DNA / Q000096:biosynthesis; D004259:DNA-Directed DNA Polymerase; D005784:Gene Amplification; D005787:Gene Frequency; D006115:Greece; D006239:Haplotypes; D006801:Humans; D009154:Mutation; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000235:genetics*
chemical_list: D004247:DNA; D010651:Phenylalanine Hydroxylase; D004259:DNA-Directed DNA Polymerase