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Mutations in the GTP cyclohydrolase I and 6‐pyruvoyl‐tetrahydropterin synthase genes
Author(s) -
Thöny Beat,
Blau Nenad
Publication year - 1997
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(1997)10:1<11::aid-humu2>3.0.co;2-p
Subject(s) - gtp cyclohydrolase i , hyperphenylalaninemia , tetrahydrobiopterin , biology , exon , genetics , compound heterozygosity , gene , biopterin , mutation , microbiology and biotechnology , nitric oxide synthase , enzyme , biochemistry , amino acid , phenylalanine
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. Hum Mutat 10:11–20, 1997. © 1997 Wiley‐Liss, Inc.