title: Two new mutations in the dihydropteridine reductase gene in patients with tetrahydrobiopterin deficiency.
abstract: Two new mutations have been identified within the dihydropteridine reductase (DHPR) gene in two patients with DHPR deficiency. The total coding sequence of the cDNA has been screened by chemical cleavage of mismatch in both patients and selected portions of the cDNA have been sequenced. The first mutation identified causes a glycine to aspartic acid substitution at codon 23 and seems particularly frequent in Mediterranean patients. Its occurrence within a glycine string common to the amino-terminal region in NADH dependent enzymes suggests a possible causal mechanism for the defect. The second change involves a tryptophan to glycine substitution at codon 108 and is carried by both alleles in the second patient. It occurs in a motif which shows similarities with a region of dihydrofolate reductase (DHFR) and is highly conserved within different animal species.
authors.affiliation: Istituto di Clinica Pediatrica, Torino, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Dianzani
authors.forename: D W
authors.initials: DW
authors.lastname: Howells
authors.forename: A
authors.initials: A
authors.lastname: Ponzone
authors.forename: J A
authors.initials: JA
authors.lastname: Saleeba
authors.forename: P M
authors.initials: PM
authors.lastname: Smooker
authors.forename: R G
authors.initials: RG
authors.lastname: Cotton
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics*; D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000235:genetics; D001483:Base Sequence; D001708:Biopterins / Q000031:analogs & derivatives* / Q000172:deficiency; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D004093:Dihydropteridine Reductase / Q000737:chemistry / Q000235:genetics*; D005998:Glycine / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009692:Nucleic Acid Heteroduplexes; D017354:Point Mutation; D014364:Tryptophan / Q000235:genetics
chemical_list: D009692:Nucleic Acid Heteroduplexes; D001708:Biopterins; D001224:Aspartic Acid; D014364:Tryptophan; D004093:Dihydropteridine Reductase; C003402:sapropterin; D005998:Glycine