Human Genetics

, Volume 104, Issue 1, pp 1–9 | Cite as

Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency

  • A. B. P. Van Kuilenburg
  • P. Vreken
  • N. G. G. M. Abeling
  • H. D. Bakker
  • R. Meinsma
  • H. Van Lenthe
  • R. A. De Abreu
  • J. A. M. Smeitink
  • H. Kayserili
  • M. Y. Apak
  • E. Christensen
  • I. Holopainen
  • K. Pulkki
  • D. Riva
  • G. Botteon
  • E. Holme
  • M. Tulinius
  • W. J. Kleijer
  • F. A. Beemer
  • M. Duran
  • K. E. Niezen-Koning
  • G. P. A. Smit
  • C. Jakobs
  • L. M. E. Smit
  • U. Moog
  • L. J. M. Spaapen
  • A. H. Van Gennip
Review article

Abstract

Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disease characterised by thymine-uraciluria in homozygous deficient patients and has been associated with a variable clinical phenotype. In order to understand the genetic and phenotypic basis for DPD deficiency, we have reviewed 17 families presenting 22 patients with complete deficiency of DPD. In this group of patients, 7 different mutations have been identified, including 2 deletions [295–298delTCAT, 1897delC], 1 splice-site mutation [IVS14+1G>A)] and 4 missense mutations (85T>C, 703C>T, 2658G>A, 2983G>T). Analysis of the prevalence of the various mutations among DPD patients has shown that the G→A point mutation in the invariant splice donor site is by far the most common (52%), whereas the other six mutations are less frequently observed. A large phenotypic variability has been observed, with convulsive disorders, motor retardation and mental retardation being the most abundant manifestations. A clear correlation between the genotype and phenotype has not been established. An altered β-alanine, uracil and thymine homeostasis might underlie the various clinical abnormalities encountered in patients with DPD deficiency.

Keywords

Uracil Thymine Splice Donor Dehydrogenase Deficiency Splice Donor Site 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • A. B. P. Van Kuilenburg
    • 1
  • P. Vreken
    • 1
  • N. G. G. M. Abeling
    • 1
  • H. D. Bakker
    • 1
  • R. Meinsma
    • 1
  • H. Van Lenthe
    • 1
  • R. A. De Abreu
    • 2
  • J. A. M. Smeitink
    • 2
  • H. Kayserili
    • 3
  • M. Y. Apak
    • 3
  • E. Christensen
    • 4
  • I. Holopainen
    • 5
  • K. Pulkki
    • 5
  • D. Riva
    • 6
  • G. Botteon
    • 6
  • E. Holme
    • 7
  • M. Tulinius
    • 7
  • W. J. Kleijer
    • 8
  • F. A. Beemer
    • 9
  • M. Duran
    • 9
  • K. E. Niezen-Koning
    • 10
  • G. P. A. Smit
    • 10
  • C. Jakobs
    • 11
  • L. M. E. Smit
    • 11
  • U. Moog
    • 12
  • L. J. M. Spaapen
    • 12
  • A. H. Van Gennip
    • 1
  1. 1.Academic Medical Center, University of Amsterdam, Emma Children’s Hospital and Department of Clinical Chemistry, PO Box 22700, 1100 DE Amsterdam, The NetherlandsNL
  2. 2.University Hospital St. Radboud, Dept. of Pediatrics, Nijmegen, The NetherlandsNL
  3. 3.University of Istanbul, Institute of Child Health, Div. Medical Genetics, Istanbul, TurkeyTR
  4. 4.Copenhagen University Hospital, Dept. of Pediatrics, Copenhagen, DenmarkDK
  5. 5.Turku University Central Hospital, Dept. of Pediatric Neurology and Dept. of Clinical Chemistry, Turku, FinlandFI
  6. 6.Instituto Nazionale Neurologico Carlo Besta, Milan, ItalyIT
  7. 7.Göteborg Universtity, Dept. of Clinical Chemistry & Transfusion Medicine and Dept. of Pediatrics, Göteborg, SwedenSE
  8. 8.Erasmus University Rotterdam, Dept. Clinical Genetics, Rotterdam, The NetherlandsNL
  9. 9.University Children’s Hospital, ‘Het Wilhelmina Kinderziekenhuis’ and Dept. of Clinical Genetics, Utrecht, The NetherlandsNL
  10. 10.University Groningen, Dept. Pediatrics, Groningen, The NetherlandsNL
  11. 11.Free University Hospital, Dept. Clinical Chemistry and Dept. of Pediatrics, Amsterdam, The NetherlandsNL
  12. 12.Maastricht University, Dept. Clinical Genetics, Maastricht, The NetherlandsNL

Personalised recommendations