Walking the ethical highwire: Genetic screening and hereditary tyrosinemia
Article first published online: 9 DEC 2005
Copyright © 1995 American Association for the Study of Liver Diseases
Volume 21, Issue 4, pages 1193–1195, April 1995
How to Cite
Romero, R. and Lavine, J. E. (1995), Walking the ethical highwire: Genetic screening and hereditary tyrosinemia. Hepatology, 21: 1193–1195. doi: 10.1002/hep.1840210444
- Issue published online: 9 DEC 2005
- Article first published online: 9 DEC 2005
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. (N Engl J Med 1994;331:353–7.)