Self-induced correction of the genetic defect in tyrosinemia type I.
Open Access
- 1 October 1994
- journal article
- Published by American Society for Clinical Investigation in Journal of Clinical Investigation
- Vol. 94 (4) , 1657-1661
- https://doi.org/10.1172/jci117509
Abstract
A mosaic pattern of immunoreactive fumarylacetoacetase (FAH) protein was found in liver tissue in 15 of 18 tyrosinemia type I patients of various ethnic origins. One additional patient had variable levels of FAH enzyme activity in liver tissue. In four patients exhibiting mosaicism of FAH protein, analysis for the tyrosinemia-causing mutations was performed in immunonegative and immunopositive areas of liver tissue by restriction digestion analysis and direct DNA sequencing. In all four patients the immunonegative liver tissue contained the FAH mutations demonstrated in fibroblasts of the patients. In the immunopositive nodules of regenerating liver tissue one of the mutated alleles apparently had reverted to the normal genotype. This genetic correction was observed for three different tyrosinemia-causing mutations. In each case a mutant AT nucleotide pair was reverted to a normal GC pair.Keywords
This publication has 5 references indexed in Scilit:
- Hereditary tyrosinemia type I. Self-induced correction of the fumarylacetoacetase defect.Journal of Clinical Investigation, 1993
- Mutations of the fumarylacetoacetate hydrolase gene in four patients with tyrosinemia, type IHuman Mutation, 1993
- Hepatic imaging with computed tomography of chronic tyrosinaemia type 1The British Journal of Radiology, 1990
- Acetylaminofluorene bound to different guanines of the sequence -GGCGCC- is excised with different efficiencies by the UvrABC excision nuclease in a pattern not correlated to the potency of mutation induction.Proceedings of the National Academy of Sciences, 1990
- DNA binding spectrum of the carcinogen N-acetoxy-N-2-acetylaminofluorene significantly differs from the mutation spectrumJournal of Molecular Biology, 1984