Structural organization and analysis of the human fumarylacetoacetate hydrolase gene in tyrosinemia type I
| Autor: | Yoshikuni Nakano, Ichiro Matsuda, Fumio Endo, A. Kitano, Hisataka Awata, Akito Tanoue |
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| Rok vydání: | 1994 |
| Předmět: |
DNA
Complementary Hydrolases Molecular Sequence Data Mutant Biology Transfection medicine.disease_cause Tyrosinemia Type I Tyrosinemia Exon Renal tubular dysfunction medicine Humans Molecular Biology Gene Cells Cultured Mutation Base Sequence Exons medicine.disease Molecular biology Biochemistry Tyrosine Molecular Medicine Fumarylacetoacetate hydrolase |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1226:168-172 |
| ISSN: | 0925-4439 |
| Popis: | Fumarylacetoacetate hydrolase (FAH) is a metabolic enzyme functioning at the last step of tyrosine catabolism. Deficiency in this enzyme activity is associated with tyrosinemia type I, characterized by hypertyrosinemia, liver dysfunction, renal tubular dysfunction, liver cirrhosis, and hepatic tumors. We isolated from a human gene library a chromosomal gene related to FAH. The human FAH gene is 30 kilobases long and is split into 14 exons. All of the splice donor and acceptor sites conform to the GT/AG rule. We also analyzed findings in a patient with tyrosinemia type I with respect to the mutation responsible for defects in the enzyme. A nucleotide change from T to G was found in the exon 2 of the gene and this change was accompanied by an amino acid substitution (Phe62Cys). Transfection and expression analysis of the cDNA in cultured BMT-10 cells with the nucleotide substitution demonstrated that the substitution was indeed responsible for the decreased activity of the enzyme in the patient. These results confirmed that the T to G mutation was one of the causes of tyrosinemia type I. Structure of the FAH gene and tests for expression of the mutant FAH will facilitate further understanding of various aspects of FAH. |
| Databáze: | OpenAIRE |
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