Novel PKU mutation on haplotype 2 in French-Canadians

Am J Hum Genet. 1989 Dec;45(6):905-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Exons
  • France / ethnology
  • Gene Amplification
  • Haplotypes*
  • Humans
  • Mutation*
  • Oligonucleotide Probes
  • Phenotype
  • Phenylalanine Hydroxylase / genetics*
  • Phenylketonurias / genetics*
  • Polymorphism, Restriction Fragment Length
  • Quebec


  • Oligonucleotide Probes
  • Phenylalanine Hydroxylase