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Keywords:

  • Phenylalanine hydroxylase;
  • Phenylketonuria;
  • Mutations;
  • DGGE

Abstract

Complete sequence analysis of 194 human phenylalanine hydroxylase genes from PKU patients originating from West Germany and Bulgaria revealed 13 different mutations within exon 7 of the gene. Four of these mutations (T238P: ACT [RIGHTWARDS ARROW] CCT; L242F: CTC [RIGHTWARDS ARROW] TTC; R252G: CGG [RIGHTWARDS ARROW] GGG; and 1043Δ11: nt 1043–nt 1053 deleted) have so far not been described in the literature. Including these new mutations at least 21 different gene lesions and one sequence polymorphism exist for exon 7. Despite this large number unbiased calculation of the mutation frequency/exon size ratio does not provide conclusive evidence that exon 7 is a hot spot for disease causing mutations. Extensive screening during our experiments also failed to demonstrate the existence of excessive polymorphism in this part of the gene. It might therefore be speculated that the functional importance of the highly conserved exon 7 sequence accounts for the clustering of observed mutations which result in clinically manifest PKU. In addition we report our experience in regard to the resolution capacity of denaturing gradient gel electrophoresis (DGGE), a nonradioactive technique for the rapid screening of unknown mutations in exon 7. © 1992 Wiley-Liss, Inc.