Identification of a Four-Base Deletion (delTCAT296-299) in the Dihydropyrimidine Dehydrogenase Gene With Variable Clinical Expression

Hum Genet. 1997 Aug;100(2):263-5. doi: 10.1007/s004390050502.


Dihydropyrimidine dehydrogenase catalyzes the first and rate-limiting step in the breakdown of thymine, uracil, and the widely used antineoplastic drug, 5-fluorouracil. Sequence analysis of the dihydropyrimidine dehydrogenase cDNA in a Dutch consanguineous family identified a novel four-base deletion (delTCAT296-299) leading to premature termination of translation. The deletion is located in a TCAT tandem-repeat sequence and most likely results from unequal crossing-over or slipped mispairing. In this family we identified three homozygous individuals for this mutation. Two of these showed convulsive disorders but one was clinically normal. This observation suggests that, at least in this family, there is no clear correlation between the dihydropyrimidine dehydrogenase genotype and phenotype.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Child, Preschool
  • DNA, Complementary / genetics
  • Dihydrouracil Dehydrogenase (NADP)
  • Female
  • Frameshift Mutation*
  • Homozygote
  • Humans
  • Male
  • Models, Genetic
  • Netherlands
  • Oxidoreductases / deficiency*
  • Oxidoreductases / genetics*
  • Polymerase Chain Reaction
  • Protein Biosynthesis
  • Purine-Pyrimidine Metabolism, Inborn Errors / etiology
  • Purine-Pyrimidine Metabolism, Inborn Errors / genetics*
  • Repetitive Sequences, Nucleic Acid
  • Seizures / etiology
  • Sequence Deletion*
  • Uracil / urine


  • DNA, Complementary
  • Uracil
  • Oxidoreductases
  • Dihydrouracil Dehydrogenase (NADP)