ArticleThe Journal of clinical investigation1992
Type 1 hereditary tyrosinemia. Evidence for molecular heterogeneity and identification of a causal mutation in a French Canadian patient.
Article in The Journal of clinical investigation, 1992. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 83 citations in OpenAlex.
- Hereditary tyrosinaemia type 1 in the absence of succinylacetone: 4-oxo 6-hydroxyhepanoate (4OHHA), a putative diagnostic biomarker.JIMD reports · 2024Article
- Biallelic variants in HPDL, encoding 4-hydroxyphenylpyruvate dioxygenase-like protein, lead to an infantile neurodegenerative condition.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- Article
- Therapeutic applications of dichloroacetate and the role of glutathione transferase zeta-1.Pharmacology & therapeutics · 2017Review
- Hedgehog signaling pathway regulates liver regeneration in the FahInternational journal of clinical and experimental pathology · 2017Article
- Validation of a multi-omics strategy for prioritizing personalized candidate driver genesOncotarget · 2016Article
- Geographical and Ethnic Distribution of Mutations of the Fumarylacetoacetate Hydrolase Gene in Hereditary Tyrosinemia Type 1.JIMD reports · 2015Article
- Heat shock response associated with hepatocarcinogenesis in a murine model of hereditary tyrosinemia type I.Cancers · 2014Article
- Clinical and para clinical findings in the children with tyrosinemia referring for liver transplantation.International journal of preventive medicine · 2013Article
- Current strategies for the treatment of hereditary tyrosinemia type I.Paediatric drugs · 2006Review
- Tyrosinaemia type I and apoptosis of hepatocytes and renal tubular cells.Journal of inherited metabolic disease · 2002Review
- Point mutations in the murine fumarylacetoacetate hydrolase gene: Animal models for the human genetic disorder hereditary tyrosinemia type 1.Proceedings of the National Academy of Sciences of the United States of America · 2001Article
- Hepatocyte injury in tyrosinemia type 1 is induced by fumarylacetoacetate and is inhibited by caspase inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 1998Article
- Therapeutic trials in the murine model of hereditary tyrosinaemia type I: a progress report.Journal of inherited metabolic disease · 1998Article
- Hereditary tyrosinemia type 1: novel missense, nonsense and splice consensus mutations in the human fumarylacetoacetate hydrolase gene; variability of the genotype-phenotype relationship.Human genetics · 1996Article
- Fungal metabolic model for human type I hereditary tyrosinaemia.Proceedings of the National Academy of Sciences of the United States of America · 1995Article
- Identification of a frequent pseudodeficiency mutation in the fumarylacetoacetase gene, with implications for diagnosis of tyrosinemia type I.American journal of human genetics · 1994Article
- Novel splice, missense, and nonsense mutations in the fumarylacetoacetase gene causing tyrosinemia type 1.American journal of human genetics · 1994Article
- Tyrosinemia type 1--complex splicing defects and a missense mutation in the fumarylacetoacetase gene.Human genetics · 1994Article
- Hereditary tyrosinemia type I: strong association with haplotype 6 in French Canadians permits simple carrier detection and prenatal diagnosis.American journal of human genetics · 1994Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 1 hereditary tyrosinemia (HT1) is a metabolic disorder caused by a deficiency of fumarylacetoacetate hydrolase (FAH). Using a full-length FAH cDNA and specific antibodies, we investigated liver specimens from seven unrelated HT1 patients (six of French Canadian and one of Scandinavian origin). The expression of FAH in livers of these individuals was analyzed at several molecular levels including mRNA, immunoreactive material (IRM), and enzymatic activity. Four phenotypic variants were differentiated by these assays: (i) presence of FAH mRNA without any IRM or enzymatic activity, (ii) decreased FAH mRNA, IRM, and enzymatic activity, (iii) moderately decreased FAH mRNA and IRM with severely reduced enzymatic activity, and (iv) undetectable FAH mRNA, IRM, and enzymatic activity. These various molecular phenotypes suggest that this disorder may be caused by a variety of FAH mutations. Interestingly, we found no apparent relationship between the clinical and the molecular phenotypes, except that patients with absent IRM and enzymatic activity tend to have higher levels of serum alpha-fetoprotein and an earlier clinical onset. To further analyze the molecular basis of HT1, the FAH cDNA of a patient designated as variant A was amplified and sequenced. An A-to-T transversion, which substitutes asparagine16 with isoleucine (N16I), was identified. This patient was heterozygous as shown by direct sequencing of the amplified region and hybridization with allele-specific oligonucleotide probes. The N16I allele originates from the father and the second allele appears not to be expressed in the liver of the proband. CV-1 cells transfected with the mutant cDNA produced FAH mRNA, but no protein or hydrolytic activity, as predicted by the "A" phenotype of the patient. This is the first demonstration of heterogeneity in the expression of FAH at the levels of protein, mRNA, and enzymatic activity in the livers of HT1 patients and is the first identification of a causal mutationin this disease.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.