title: Mutations in the GTP cyclohydrolase I and 6-pyruvoyl-tetrahydropterin synthase genes.
abstract: Tetrahydrobiopterin deficiencies are highly heterogeneous disorders, with more than 30 molecular lesions identified in the past 2 years in the GTP cyclohydrolase I and 6-pyruvoyl-tetrahydropterin synthase genes. The spectrum of mutations causing a reduction of these two biosynthetic enzymes is reviewed. Only three mutations, two present homozygously, are reported in the GTP cyclohydrolase I gene to cause the rare autosomal recessively inherited form of hyperphenylalaninemia. Most of the other mutations, which are scattered over the entire coding region for the six exon-containing GTP cyclohydrolase I gene, are observed in a heterozygous state with the wild-type allele and are associated with the dominant DOPA-responsive dystonia. Compound heterozygous or homozygous mutations spread over all six exons encoding the 6-pyruvoyl-tetrahydropterin synthase cause an autosomal recessively inherited variant of hyperphenylalaninemia, mostly accompanied by a deficiency of dopamine and serotonin.
authors.affiliation: Division of Clinical Chemistry and Biochemistry, University Children's Hospital, Zurich, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Thöny
authors.forename: N
authors.initials: N
authors.lastname: Blau
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics*; D000483:Alleles; D001708:Biopterins / Q000031:analogs & derivatives* / Q000172:deficiency / Q000378:metabolism; D006136:GTP Cyclohydrolase / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D019761:Phosphorus-Oxygen Lyases; D011110:Polymorphism, Genetic / Q000235:genetics; D012326:RNA Splicing / Q000235:genetics
chemical_list: D001708:Biopterins; D000429:Alcohol Oxidoreductases; D006136:GTP Cyclohydrolase; D019761:Phosphorus-Oxygen Lyases; C043497:6-pyruvoyltetrahydropterin synthase; C003402:sapropterin