Phenylalanine hydroxylase gene mutations in phenylketonuria patients from India: identification of novel mutations that affect PAH RNA

Mol Genet Metab. 2010 May;100(1):96-9. doi: 10.1016/j.ymgme.2010.01.016. Epub 2010 Feb 2.

Abstract

Analysis of seven Indian phenylketonuria families has revealed four novel mutations in the phenylalanine hydroxylase gene; two affected consensus splice sequence and the 3' UTR, respectively, while the other two were single base insertion and deletion mutations, respectively. A novel 3' splice site mutation c.168-2A>G resulted in the activation of a cryptic 3' splice site that generated a premature termination codon leading to very low levels of the mutant transcript, probably due to activation of the nonsense-mediated decay (NMD) pathway. This is probably the first report of PKU caused by the activation of NMD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Male
  • Mutation
  • Phenylalanine Hydroxylase / genetics*
  • Phenylketonurias / enzymology
  • Phenylketonurias / genetics*
  • RNA Splice Sites
  • Sequence Deletion

Substances

  • RNA Splice Sites
  • Phenylalanine Hydroxylase