The phenylketonuria locus: current knowledge about alleles and mutations of the phenylalanine hydroxylase gene in various populations

Hum Genet. 1991 Aug;87(4):377-88. doi: 10.1007/BF00197152.


The hyperphenylalaninemic disorders of classic phenylketonuria (PKU), mild phenylketonuria, and hyperphenylalaninemia (HPA), result from a deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH) or its cofactor (tetrahydrobiopterin). Use of the complementary DNA of this enzyme has allowed the establishment of a restriction fragment length polymorphism (RFLP) haplotype-analysis system. This haplotype analysis system provides the means for determination of mutant PAH alleles in most affected families and is the basis for mutational analysis of the PKU locus. This review is focused on two major areas of current PKU research: (1) the use of DNA haplotype analysis in the study of the population genetics of PAH deficiency, and (2) the study of genotypes, and their various combinations, as a means of explaining and predicting the phenotypic variability observed for the disorders of PAH deficiency.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alleles*
  • Chromosome Mapping
  • Genetics, Population*
  • Haplotypes
  • Humans
  • Mutation*
  • Phenylalanine Hydroxylase / deficiency
  • Phenylalanine Hydroxylase / genetics*
  • Phenylketonurias / genetics*
  • Polymorphism, Restriction Fragment Length


  • Phenylalanine Hydroxylase