A single mutation of the fumarylacetoacetate hydrolase gene in French Canadians with hereditary tyrosinemia type I

N Engl J Med. 1994 Aug 11;331(6):353-7. doi: 10.1056/NEJM199408113310603.


Background: Hereditary tyrosinemia type I is an autosomal recessive inborn error of metabolism caused by a deficiency of the enzyme fumarylacetoacetate hydrolase. The disorder clusters in the Saguenay-Lac-St.-Jean area of Quebec. In this region, 1 of 1846 newborns is affected and 1 of every 22 persons is thought to be a carrier. Recently, we identified a splice mutation and two nonsense mutations in the fumarylacetoacetate hydrolase gene in two patients from Quebec with tyrosinemia type I.

Methods: We used allele-specific-oligonucleotide hybridization to examine the frequency of these three candidate mutations in patients with tyrosinemia type I and in the population of Quebec.

Results: The splice mutation was found in 100 percent of patients from the Saguenay-Lac-St.-Jean area and in 28 percent of patients from other regions of the world. Of 25 patients from the Saguenay-Lac-St.-Jean region, 20 (80 percent) were homozygous for this mutation, a guanine-to-adenine change in the splice-donor sequence in intron 12 of the gene, indicating that it causes most cases of tyrosinemia type I in the region. The frequency of carrier status, based on screening of blood spots from newborns, was about 1 per 25 in the Saguenay-Lac-St.-Jean population and about 1 per 66 overall in Quebec.

Conclusions: This study identified the most prevalent mutation causing hereditary tyrosinemia in French Canada; it also showed the feasibility of DNA-based testing for carriers in the population at risk.

Publication types

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

MeSH terms

  • Alleles*
  • Amino Acid Metabolism, Inborn Errors / enzymology
  • Amino Acid Metabolism, Inborn Errors / genetics*
  • Base Sequence
  • DNA Primers
  • Feasibility Studies
  • Heterozygote
  • Humans
  • Hydrolases / genetics*
  • Infant, Newborn
  • Molecular Sequence Data
  • Mutation*
  • Polymerase Chain Reaction
  • Quebec
  • Tyrosine / blood*
  • Tyrosine / genetics


  • DNA Primers
  • Tyrosine
  • Hydrolases
  • fumarylacetoacetase