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Previous Volume 331:353-357 August 11, 1994 Number 6 Next

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ABSTRACT

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. .

Source Information

From the Department of Molecular and Medical Genetics and the Department of Pediatrics, Oregon Health Sciences University, Portland (M.G., M.A.-D.); and the Laboratoire de genetique cellulaire et moleculaire, Medicine Genetique et Moleculaire, Centre de recherche du Centre Hospitalier de l'Universite Laval, Ste.-Foy, Quebec (M.S.-L., S.I.D., B.L., R.M.T.).

Address reprint requests to Dr. Grompe at the Department of Molecular and Medical Genetics, Mail Code L103, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Rd., Portland, OR 97201-3098.

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