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Fumarylacetoacetase mutations in tyrosinaemia type I
Author(s) -
Rootwelt Helge,
Høie Kari,
Berger Ruud,
Kvittingen Eli Anne
Publication year - 1996
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1996)7:3<239::aid-humu8>3.0.co;2-5
Subject(s) - genetics , biology , allele , missense mutation , genotype , mutation , phenotype , gene , splice site mutation , genomic dna , compound heterozygosity , rna splicing , rna
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. © 1996 Wiley‐Liss, Inc.