Spectrum of mutations in the fumarylacetoacetate hydrolase gene of tyrosinemia type 1 patients in northwestern Europe and Mediterranean countries
- 1 January 1998
- journal article
- research article
- Published by Hindawi Limited in Human Mutation
- Vol. 12 (1) , 19-26
- https://doi.org/10.1002/(sici)1098-1004(1998)12:1<19::aid-humu3>3.0.co;2-3
Abstract
Hereditary tyrosinemia type 1 (HT1) is a rare metabolic disease caused by a deficient activity of the enzyme fumarylacetoacetase (FAH). To investigate the molecular heterogeneity of tyrosinemia, the geographic distribution and the genotype–phenotype relationship, we have analyzed the FAH genotype of 25 HT1 patients. Mutation screening was performed by PCR amplification of exons 1‐14 of the FAH gene, followed by SSCP analysis and direct sequencing of the amplified exons. Fourteen different mutations were found, of which seven were novel, viz. Three missense mutations (G158D, P261L, F405H), a deletion of three nucleotides causing a deletion of serine (DEL366S) and three splice site mutations: IVS2+1(g‐t), IVS6‐1(g‐c), IVS8‐1(g‐c). The splice site mutations IVS6‐1(g‐t) and IVS12+5(g‐a) were frequently found in countries around the Mediterranean and northerwestern Europe, respectively. No clear correlation between the genotype and the three major HT1 subtypes could be established. Hum Mutat 12:19–26, 1998.Keywords
This publication has 19 references indexed in Scilit:
- Hepatocytes corrected by gene therapy are selected in vivo in a murine model of hereditary tyrosinaemia type INature Genetics, 1996
- Hereditary tyrosinemia type 1: novel missense, nonsense and splice consensus mutations in the human fumarylacetoacetate hydrolase gene; variability of the genotype-phenotype relationshipHuman Genetics, 1996
- Self-induced correction of the genetic defect in tyrosinemia type I.Journal of Clinical Investigation, 1994
- A Single Mutation of the Fumarylacetoacetate Hydrolase Gene in French Canadians with Hereditary Tyrosinemia Type INew England Journal of Medicine, 1994
- Two missense mutations causing tyrosinemia type 1 with presence and absence of immunoreactive fumarylacetoacetaseHuman Genetics, 1994
- Structural organization and analysis of the human fumarylacetoacetate hydrolase gene in tyrosinemia type IBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1994
- Characterization of the human fumarylacetoacetate hydrolase gene and identification of a missense mutation abolishing enzymatic activityHuman Molecular Genetics, 1993
- 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
- Type 1 hereditary tyrosinemia. Evidence for molecular heterogeneity and identification of a causal mutation in a French Canadian patient.Journal of Clinical Investigation, 1992