title: 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.
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.
authors.affiliation: Centre de Recherche du CHUL, Université Laval, Ste-Foy, Québec, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Poudrier
authors.forename: M
authors.initials: M
authors.lastname: St-Louis
authors.forename: F
authors.initials: F
authors.lastname: Lettre
authors.forename: K
authors.initials: K
authors.lastname: Gibson
authors.forename: C
authors.initials: C
authors.lastname: Prévost
authors.forename: J
authors.initials: J
authors.lastname: Larochelle
authors.forename: R M
authors.initials: RM
authors.lastname: Tanguay
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D006867:Hydrolases / Q000172:deficiency* / Q000235:genetics*; D008297:Male; D009154:Mutation; D011792:Quebec; D012326:RNA Splicing; D014443:Tyrosine / Q000097:blood*
chemical_list: D014443:Tyrosine; D006867:Hydrolases; C020156:fumarylacetoacetase