The Experts below are selected from a list of 9 Experts worldwide ranked by ideXlab platform
John Hilton - One of the best experts on this subject based on the ideXlab platform.
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the molecular basis of Glutamate Formiminotransferase deficiency
Human Mutation, 2003Co-Authors: John Hilton, Karen E Christensen, David Watkins, Benjamin A Raby, Yannick Renaud, Susanna De La Luna, Xavier Estivill, Robert E MackenzieAbstract:Glutamate Formiminotransferase deficiency, an autosomal recessive disorder and the second most common inborn error of folate metabolism, is presumed to be due to defects in the bifunctional enzyme Glutamate Formiminotransferase-cyclodeaminase (FTCD). Features of a severe phenotype, first identified in patients of Japanese descent, include elevated levels of formiminoGlutamate (FIGLU) in the urine in response to histidine administration, megaloblastic anemia, and mental retardation. Features of a mild phenotype include high urinary excretion of FIGLU in the absence of histidine administration, mild developmental delay, and no hematological abnormalities. We found mutations in the human FTCD gene in three patients with putative Glutamate Formiminotransferase deficiency. Two siblings were heterozygous for missense mutations, c.457C>T (R135C) and c.940G>C (R299P). Mutagenesis of porcine FTCD and expression in E. coli showed that the R135C mutation reduced Formiminotransferase activity to 61% of wild-type, whereas the R299P mutation reduced this activity to 57% of wild-type. The third patient was hemizygous for c.1033insG, with quantitative PCR indicating that the other allele contained a deletion. These mutations are the first identified in Glutamate Formiminotransferase deficiency and demonstrate that mutations in FTCD represent the molecular basis for the mild phenotype of this disease. Hum Mutat 22:67–73, 2003. © 2003 Wiley-Liss, Inc.
Robert E Mackenzie - One of the best experts on this subject based on the ideXlab platform.
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the molecular basis of Glutamate Formiminotransferase deficiency
Human Mutation, 2003Co-Authors: John Hilton, Karen E Christensen, David Watkins, Benjamin A Raby, Yannick Renaud, Susanna De La Luna, Xavier Estivill, Robert E MackenzieAbstract:Glutamate Formiminotransferase deficiency, an autosomal recessive disorder and the second most common inborn error of folate metabolism, is presumed to be due to defects in the bifunctional enzyme Glutamate Formiminotransferase-cyclodeaminase (FTCD). Features of a severe phenotype, first identified in patients of Japanese descent, include elevated levels of formiminoGlutamate (FIGLU) in the urine in response to histidine administration, megaloblastic anemia, and mental retardation. Features of a mild phenotype include high urinary excretion of FIGLU in the absence of histidine administration, mild developmental delay, and no hematological abnormalities. We found mutations in the human FTCD gene in three patients with putative Glutamate Formiminotransferase deficiency. Two siblings were heterozygous for missense mutations, c.457C>T (R135C) and c.940G>C (R299P). Mutagenesis of porcine FTCD and expression in E. coli showed that the R135C mutation reduced Formiminotransferase activity to 61% of wild-type, whereas the R299P mutation reduced this activity to 57% of wild-type. The third patient was hemizygous for c.1033insG, with quantitative PCR indicating that the other allele contained a deletion. These mutations are the first identified in Glutamate Formiminotransferase deficiency and demonstrate that mutations in FTCD represent the molecular basis for the mild phenotype of this disease. Hum Mutat 22:67–73, 2003. © 2003 Wiley-Liss, Inc.
Benjamin A Raby - One of the best experts on this subject based on the ideXlab platform.
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the molecular basis of Glutamate Formiminotransferase deficiency
Human Mutation, 2003Co-Authors: John Hilton, Karen E Christensen, David Watkins, Benjamin A Raby, Yannick Renaud, Susanna De La Luna, Xavier Estivill, Robert E MackenzieAbstract:Glutamate Formiminotransferase deficiency, an autosomal recessive disorder and the second most common inborn error of folate metabolism, is presumed to be due to defects in the bifunctional enzyme Glutamate Formiminotransferase-cyclodeaminase (FTCD). Features of a severe phenotype, first identified in patients of Japanese descent, include elevated levels of formiminoGlutamate (FIGLU) in the urine in response to histidine administration, megaloblastic anemia, and mental retardation. Features of a mild phenotype include high urinary excretion of FIGLU in the absence of histidine administration, mild developmental delay, and no hematological abnormalities. We found mutations in the human FTCD gene in three patients with putative Glutamate Formiminotransferase deficiency. Two siblings were heterozygous for missense mutations, c.457C>T (R135C) and c.940G>C (R299P). Mutagenesis of porcine FTCD and expression in E. coli showed that the R135C mutation reduced Formiminotransferase activity to 61% of wild-type, whereas the R299P mutation reduced this activity to 57% of wild-type. The third patient was hemizygous for c.1033insG, with quantitative PCR indicating that the other allele contained a deletion. These mutations are the first identified in Glutamate Formiminotransferase deficiency and demonstrate that mutations in FTCD represent the molecular basis for the mild phenotype of this disease. Hum Mutat 22:67–73, 2003. © 2003 Wiley-Liss, Inc.
Xavier Estivill - One of the best experts on this subject based on the ideXlab platform.
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the molecular basis of Glutamate Formiminotransferase deficiency
Human Mutation, 2003Co-Authors: John Hilton, Karen E Christensen, David Watkins, Benjamin A Raby, Yannick Renaud, Susanna De La Luna, Xavier Estivill, Robert E MackenzieAbstract:Glutamate Formiminotransferase deficiency, an autosomal recessive disorder and the second most common inborn error of folate metabolism, is presumed to be due to defects in the bifunctional enzyme Glutamate Formiminotransferase-cyclodeaminase (FTCD). Features of a severe phenotype, first identified in patients of Japanese descent, include elevated levels of formiminoGlutamate (FIGLU) in the urine in response to histidine administration, megaloblastic anemia, and mental retardation. Features of a mild phenotype include high urinary excretion of FIGLU in the absence of histidine administration, mild developmental delay, and no hematological abnormalities. We found mutations in the human FTCD gene in three patients with putative Glutamate Formiminotransferase deficiency. Two siblings were heterozygous for missense mutations, c.457C>T (R135C) and c.940G>C (R299P). Mutagenesis of porcine FTCD and expression in E. coli showed that the R135C mutation reduced Formiminotransferase activity to 61% of wild-type, whereas the R299P mutation reduced this activity to 57% of wild-type. The third patient was hemizygous for c.1033insG, with quantitative PCR indicating that the other allele contained a deletion. These mutations are the first identified in Glutamate Formiminotransferase deficiency and demonstrate that mutations in FTCD represent the molecular basis for the mild phenotype of this disease. Hum Mutat 22:67–73, 2003. © 2003 Wiley-Liss, Inc.
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cloning and characterization of human ftcd on 21q22 3 a candidate gene for Glutamate Formiminotransferase deficiency
Cytogenetic and Genome Research, 2000Co-Authors: A Solans, Xavier Estivill, S De La LunaAbstract:We have identified a new human gene, FTCD, which maps to chromosome 21q22.3 and encodes the enzyme Formiminotransferase cyclodeaminase, an intermediate metabolism enzyme that links histidine catabolism to folate metabolism. The major cDNA encodes a protein containing 541 amino acid residues and shows 84% identity with porcine FTCD. Several other cDNAs have been isolated, which may result from alternative splicing events and have the potential to code for three different protein isoforms. The gene is highly expressed in human fetal and adult liver. The two FTCD protein domains show high sequence similarity to two distinct open reading frames from eubacterial genomes, suggesting that eukaryotic FTCD appeared through a gene fusion event. Defects in the Glutamate Formiminotransferase pathway have been documented, and the deficiency is presumed to be inherited as an autosomal recessive trait. The sequence reported here may be helpful in identifying the primary defect in Glutamate Formiminotransferase deficiency and establishing a molecular diagnosis.
Karen E Christensen - One of the best experts on this subject based on the ideXlab platform.
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the molecular basis of Glutamate Formiminotransferase deficiency
Human Mutation, 2003Co-Authors: John Hilton, Karen E Christensen, David Watkins, Benjamin A Raby, Yannick Renaud, Susanna De La Luna, Xavier Estivill, Robert E MackenzieAbstract:Glutamate Formiminotransferase deficiency, an autosomal recessive disorder and the second most common inborn error of folate metabolism, is presumed to be due to defects in the bifunctional enzyme Glutamate Formiminotransferase-cyclodeaminase (FTCD). Features of a severe phenotype, first identified in patients of Japanese descent, include elevated levels of formiminoGlutamate (FIGLU) in the urine in response to histidine administration, megaloblastic anemia, and mental retardation. Features of a mild phenotype include high urinary excretion of FIGLU in the absence of histidine administration, mild developmental delay, and no hematological abnormalities. We found mutations in the human FTCD gene in three patients with putative Glutamate Formiminotransferase deficiency. Two siblings were heterozygous for missense mutations, c.457C>T (R135C) and c.940G>C (R299P). Mutagenesis of porcine FTCD and expression in E. coli showed that the R135C mutation reduced Formiminotransferase activity to 61% of wild-type, whereas the R299P mutation reduced this activity to 57% of wild-type. The third patient was hemizygous for c.1033insG, with quantitative PCR indicating that the other allele contained a deletion. These mutations are the first identified in Glutamate Formiminotransferase deficiency and demonstrate that mutations in FTCD represent the molecular basis for the mild phenotype of this disease. Hum Mutat 22:67–73, 2003. © 2003 Wiley-Liss, Inc.