title: Novel PKU mutation on haplotype 2 in French-Canadians.
abstract: We analyzed DNA from nine French-Canadian probands from eastern Quebec province; all had hyperphenylalaninemia (phenylketonuria [PKU] or non-PKU forms) caused by mutations at the phenylalanine hydroxylase locus. Analysis of RFLP haplotypes and mutations revealed a novel mutation, an A-to-G transition (met----val) in codon 1 (the translation-initiation codon). It occurred on 5 of the 18 mutant chromosomes and was associated each time with haplotype 2. A proband homozygous for this mutation had the PKU phenotype. In other probands, the codon 1 mutation was inherited once with the splice junction mutation in exon 12 (on haplotype 3), conferring PKU, and was inherited twice with a mutation on haplotype 1, conferring PKU in one proband and non-PKU hyperphenylalaninemia in the other. The other five probands carried mutations, conferring PKU, on the following haplotype combinations: 1/3 (twice), 1/9, 3/4, and 1/1. The mutations on haplotypes 1, 4, and 9 are not yet characterized. This preliminary study reveals a novel PKU mutation and considerable genetic heterogeneity at the phenylalanine hydroxylase locus in French-Canadians.
authors.affiliation: Department of Biology, McGill University, Montreal, Quebec.
authors.forename: S W
authors.initials: SW
authors.lastname: John
authors.forename: R
authors.initials: R
authors.lastname: Rozen
authors.forename: R
authors.initials: R
authors.lastname: Laframboise
authors.forename: C
authors.initials: C
authors.lastname: Laberge
authors.forename: C R
authors.initials: CR
authors.lastname: Scriver
mesh_terms: D005091:Exons; D005602:France / Q000208:ethnology; D005784:Gene Amplification; D006239:Haplotypes; D006801:Humans; D009154:Mutation; D015345:Oligonucleotide Probes; D010641:Phenotype; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011792:Quebec
chemical_list: D015345:Oligonucleotide Probes; D010651:Phenylalanine Hydroxylase