Frequency of the IVS12 + 5G-->A splice mutation of the fumarylacetoacetate hydrolase gene in carriers of hereditary tyrosinaemia in the French Canadian population of Saguenay-Lac-St-Jean

Prenat Diagn. 1996 Jan;16(1):59-64. doi: 10.1002/(SICI)1097-0223(199601)16:1<59::AID-PD810>3.0.CO;2-D.

Abstract

Hereditary tyrosinaemia type I (HTI), an autosomal recessive inborn error of metabolism, is caused by a deficiency of the enzyme fumarylacetoacetate hydrolase. The highest incidence of HTI is observed in the Saguenay-Lac-St-Jean region (SLSJ) (Québec, Canada), where 1 out of 22 individuals is thought to be a carrier. A splice mutation (IVS12 + 5G-->A) has recently been identified in this particular region. Here, we have determined the frequency of this mutation in a population of obligate carriers from the SLSJ region by allele-specific oligonucleotide hybridization and a method using a restriction enzyme digestion. Over 95 per cent of the HTI carriers were found to have the IVS12 + 5G-->A splice mutation. Screening for this mutation based on the two methods reported here is thus a reliable and rapid way of detecting carriers of hereditary tyrosinaemia type I in that region at high risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / genetics*
  • Female
  • Gene Frequency
  • Heterozygote*
  • Humans
  • Hydrolases / deficiency*
  • Hydrolases / genetics*
  • Male
  • Mutation*
  • Quebec
  • RNA Splicing*
  • Tyrosine / blood*

Substances

  • Tyrosine
  • Hydrolases
  • fumarylacetoacetase