title: Fumarylacetoacetase mutations in tyrosinaemia type I.
abstract: Sixty-two hereditary tyrosinaemia type I (HT1) patients of various ethnic origins were classified clinically into acute, chronic, or intermediate phenotypes and screened for the 14 published causal mutations in the fumarylacetoacetase (FAH) gene. Restriction analysis of PCR amplified genomic DNA identified 74% of the mutated alleles. IVS12 + 5G --> A, predominant in the French Canadian HT1 patients, was the most common mutation found in 32 alleles in patients from Europe, Pakistan, Turkey, and the United States. IVS6-1G --> T, encountered in 14 alleles, was common in Central and Western Europe. There was an apparent "Scandinavian" 1009G --> A combined splice and missense mutation (12 alleles), a "Pakistani" 192G --> T splice mutation (11 alleles), a "Turkish" D233V mutation (6 alleles), and a "Finnish" or northern European W262X mutation (7 alleles). The remaining mutations were rare. Some of the mutations seem to predispose for acute and other for more chronic forms of HT1, but in our material no clearcut genotype phenotype correlation could be established.
authors.affiliation: Institute of Clinical Biochemistry, University of Oslo, Rikshospitalet, Norway.
authors.forename: H
authors.initials: H
authors.lastname: Rootwelt
authors.forename: K
authors.initials: K
authors.lastname: Høie
authors.forename: R
authors.initials: R
authors.lastname: Berger
authors.forename: E A
authors.initials: EA
authors.lastname: Kvittingen
mesh_terms: D000483:Alleles; D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics*; D001483:Base Sequence; D017931:DNA Primers; D004587:Electrophoresis, Agar Gel; D005838:Genotype; D006801:Humans; D006867:Hydrolases / Q000737:chemistry / Q000172:deficiency / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012326:RNA Splicing / Q000235:genetics; D014443:Tyrosine / Q000097:blood*
chemical_list: D017931:DNA Primers; D014443:Tyrosine; D006867:Hydrolases; C020156:fumarylacetoacetase