TY - JOUR
T1 - Spectrum of mutations in the fumarylacetoacetate hydrolase gene of tyrosinemia type 1 patients in northwestern Europe and Mediterranean countries
AU - Bergman, A. J.
AU - van den Berg, I. E.
AU - Brink, W.
AU - Poll-The, B. T.
AU - Ploos van Amstel, J. K.
AU - Berger, R.
PY - 1998
Y1 - 1998
N2 - 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 northwestern Europe, respectively. No clear correlation between the genotype and the three major HT1 subtypes could be established
AB - 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 northwestern Europe, respectively. No clear correlation between the genotype and the three major HT1 subtypes could be established
U2 - https://doi.org/10.1002/(SICI)1098-1004(1998)12:1<19::AID-HUMU3>3.0.CO;2-3
DO - https://doi.org/10.1002/(SICI)1098-1004(1998)12:1<19::AID-HUMU3>3.0.CO;2-3
M3 - Article
C2 - 9633815
SN - 1059-7794
VL - 12
SP - 19
EP - 26
JO - Human mutation
JF - Human mutation
IS - 1
ER -