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Spectrum of mutations in the fumarylacetoacetate hydrolase gene of tyrosinemia type 1 patients in northwestern Europe and Mediterranean countries
Author(s) -
Bergman AJIW,
van den Berg IET,
Brink W,
PollThe BT,
Ploos van Amstel JK,
Berger R
Publication year - 1998
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(1998)12:1<19::aid-humu3>3.0.co;2-3
Subject(s) - biology , genetics , missense mutation , exon , tyrosinemia , genotype , gene , splice , mutation , genotype phenotype distinction , single strand conformation polymorphism , microbiology and biotechnology , tyrosine , biochemistry
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. © 1998 Wiley‐Liss, Inc.