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Journal of Inherited Metabolic Disease

, Volume 19, Issue 5, pp 645–654 | Cite as

A point mutation in an invariant splice donor site leads to exon skipping in two unrelated Dutch patients with dihydropyrimidine dehydrogenase deficiency

  • P. Vreken
  • A. B. P. Van Kuilenburg
  • R. Meinsma
  • G. P. A. Smit
  • H. D. Bakker
  • R. A. De Abreu
  • A. H. van Gennip
Article

Summary

Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disease characterized by thymine-uraciluria and associated with a variable clinical phenotype. In order to identify the molecular defect underlying complete DPD deficiency in a Dutch patient previously shown to have a 165 base pair deletion in the mature DPD mRNA, we cloned the genomic region encompassing the skipped exon and its flanking intron sequences. Sequence analysis revealed that the patient was homozygous for a single G→A point mutation in the invariant GT dinucleotide splice donor site downstream of the skipped exon. The same mutation was identified in another, unrelated, Dutch patient. Because this mutation destroys a uniqueMaeII restriction site, rapid screening using restriction enzyme cleavage of the amplified genomic region encompassing this mutation is possible. Analysis of 50 controls revealed no individuals heterozygous for this mutation

Keywords

Dinucleotide Enzyme Cleavage Dehydrogenase Deficiency Splice Donor Site Molecular Defect 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© SSIEM and Kluwer Academic Publishers 1996

Authors and Affiliations

  • P. Vreken
    • 1
  • A. B. P. Van Kuilenburg
    • 1
  • R. Meinsma
    • 1
  • G. P. A. Smit
    • 2
  • H. D. Bakker
    • 1
  • R. A. De Abreu
    • 3
  • A. H. van Gennip
    • 1
  1. 1.Academic Medical CenterUniversity of Amsterdam, Department of Clinical Chemistry F0-224AmsterdamThe Netherlands
  2. 2.Department of PediatricsAcademic Hospital GroningenGroningen
  3. 3.Department of PediatricsAcademic Hospital NijmegenNjmegenThe Netherlands

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