2 NEW MUTATIONS IN THE DIHYDROPTERIDINE REDUCTASE GENE IN PATIENTS WITH TETRAHYDROBIOPTERIN DEFICIENCY

Two new mutations have been identified within the dihydropteridine red uctase (DHPR) gene in two patients with DHPR deficiency. The total cod ing sequence of the cDNA has been screened by chemical cleavage of mis match in both patients and selected portions of the cDNA have been seq uenced. The first mutation identified causes a glycine to aspartic aci d substitution at codon 23 and seems particularly frequent in Mediterr anean patients. Its occurrence within a glycine string common to the a mino-terminal region in NADH dependent enzymes suggests a possible cau sal 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 wit h a region of dihydrofolate reductase (DHFR) and is highly conserved w ithin different animal species.