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.
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.
Poudrier
J
J
Centre de Recherche du CHUL, Université Laval, Ste-Foy, Québec, Canada.
St-Louis
M
M
Lettre
F
F
Gibson
K
K
Prévost
C
C
Larochelle
J
J
Tanguay
R M
RM
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*
D014443:Tyrosine; D006867:Hydrolases; C020156:fumarylacetoacetase