Identification of novel point mutations in the dihydropyrimidine dehydrogenase gene

摘要: Dihydropyrimidine dehydrogenase deficiency (McKusick 274270) is an autosomal recessive disorder leading to thymine-uraciluria. (DPD; EC 1.3.1.2) catalyses the first and rate-limiting step in catabolism of uracil, thymine analogue 5-fluorouracil. Patients do not exhibit a characteristic clinical phenotype, although about half cases with complete or near-complete enzyme convulsive disorders are observed (Berger et al 1984; van Gennip 1989, 1994; Braakhekke 1987). In patients nearly defect, initial diagnosis can be made on presence large amounts both uracil patient's body fluids, whereas confirmed by measurement activity either peripheral mononuclear cells fibroblasts (Van Kuilenburg 1996). The recent cloning dihydropyrimidine cDNA now allows detection defect at molecular level (Yokota 1994). We previously described 165 base pair deletion mRNA-derived cDNA, caused exon skipping, patient DPD (Meinsma 1995). Analysis flanking intron sequences revealed that skipping was due G → A point mutation invariant GT splice donor sequence downstream skipped (Vreken So far, no other mutations gene have been described. report new frameshift (ΔC1897) two missense (T85C G2658A) amino acid substitutions C29R R886H.