European Journal of Pediatrics

, Volume 147, Issue 4, pp 368–371 | Cite as

DNA analysis of ornithine transcarbamylase deficiency

  • U. Wendel
  • E. Wilichowski
  • J. Schmidtke
  • C. Bachmann
Original Investigations

Abstract

By analysing the restriction fragment length polymorphism (RFLP) detected by an ornithinetranscarbamylase (OTC) gene specific DNA probe, we followed the segregation of the defective gene in two families with OTC deficiency (X-linked disease). We were able to exclude some female family members as carriers. In one case a doubtful result obtained in a biochemical carrier detection test (by examining the renal orotic acid excretion after a protein load) could be clarified by DNA analysis. In every family with OTC deficiency, carrier detection should be biochemical with additional DNA analysis. Previous results of the biochemical carrier test should be controlled by DNA analysis, especially when “normal” results were obtained.

Key words

Ornithintranscarbamylase deficiency Carrier detection DNA analysis Segregation analysis 

Abbreviations

OTC

ornithinetranscarbamylase

RFLP

restriction fragment length polymorphism

DNA

desoxyribonucleic acid

cDNA

complementary DNA

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References

  1. 1.
    Adachi T, Tanimura A, Asahina M (1963) A colorimetric determination of orotic acid. J Vitaminol 9:217–226Google Scholar
  2. 2.
    Amir J, Alpert G, Statter M, Gutman A, Reisner SH (1982) Intracranial haemorrhage in siblings and ornithine transcarbamylase deficiency. Acta Paediatr Scand 71:671–673Google Scholar
  3. 3.
    Bachmann C, Colombo JP (1980) Diagnostic value of orotic acid excretion in heritable disorders of the urea cycle and in hyperammonemia due to organic acidurias. Eur J Pediatr 134:109–113Google Scholar
  4. 4.
    Bachmann C, Colombo JP (1980) Determination of orotic acid in children's urine. J Clin Chem Clin Biochem 18:293–295Google Scholar
  5. 5.
    Bachmann C, Colombo JP (1982) Orotic acid in urine and hyperammonemia. Adv Exp Med Biol 153:313–319Google Scholar
  6. 6.
    Batshaw ML, Msall M, Beaudet AL, Trojak J (1986) Risk of serious illness in heterozygotes for ornithine transcarbamylase deficiency. J Pediatr 108:236–241Google Scholar
  7. 7.
    Becroft DMO, Barry DMJ, Webster DR, Simmonds HA (1984) Failure of protein loading tests to identify heterozygosity for ornithine carbamoyltransferase deficiency. J Inherited Metab Dis 7:157–159Google Scholar
  8. 8.
    Brubakk A-M, Teijema LL, Blom W, Berger R (1982) Successful treatment of severe OTC deficiency. J Pediatr 100:929–931Google Scholar
  9. 9.
    Di Magno EP, Lowe JE, Snodgrass PJ, Jones JD (1986) Ornithine transcarbamylase deficiency — a cause of bizarre behavior in a man. N Engl J Med 315:744–748Google Scholar
  10. 10.
    Fox J, Hack AM, Fenton WA, Golbus MS, Winter S, Kalousek F, Rozen R, Brusilow SW, Rosenberg LE (1986) Prenatal diagnosis of ornithine transcarbamylase deficiency with use of DNA polymorphisms. N Engl J Med 315:1205–1208Google Scholar
  11. 11.
    Glasgow AM, Kraegel JK, Schulman JD (1978) Studies of the cause and treatment of hyperammonemia in females with ornithine transcarbamylase deficiency. Pediatrics 62:30–37Google Scholar
  12. 12.
    Goldstein AS, Hoogenraad NJ, Johnson JD, Fikanaga K, Swierczewski E, Cann HM, Sunshine P (1974) Metabolic and genetic studies of a family with ornithine transcarbamylase deficiency. Pediatr Res 8:5–12Google Scholar
  13. 13.
    Guibaud P, Baxter P, Bourgeous J, Louis JJ, Bureau J (1984) Severe ornithine transcarbamylase dificiency. Two and a half years' survival with normal development. Arch Dis Child 59:477–479Google Scholar
  14. 14.
    Haan EA, Danks DM, Grimes A, Hoogenraad NJ (1982) Carrier detection in ornithine transcarbamylase deficiency. J Inherited Metab Dis 5:37–40Google Scholar
  15. 15.
    Hokanson JT, O'Brien WE, Idemoto J, Schafer IA (1978) Carrier detection in ornithine transcarbamylase deficiency. J Pediatr 93:75–78Google Scholar
  16. 16.
    Holzgreve W, Golbus MS (1984) Prenatal diagnosis of ornithine transcarbamylase deficiency utilizing fetal liver biopsy. Am J Hum Gene 36:320–328Google Scholar
  17. 17.
    Horwich HL, Fenton WA, Williams KR, Kalousek F, Kraus JP (1984) Structure and expression of a complementary DNA for the nuclear coded precursor of human mitochondrial ornithine transcarbamylase. Science 224:1068–1074Google Scholar
  18. 18.
    Lyon MF (1962) Sex chromatine and gene action in the mammalian X-chromosome. Am J Hum Genet 14:135–148Google Scholar
  19. 19.
    Maniatis T, Fritsch EF, Sambrook J (1982) Molecular cloning. A laboratory manual. Cold Spring Harbour Laboratory Press, New YorkGoogle Scholar
  20. 20.
    McClead RE, Rozen R, Fox J, Rosenberg L, Menke J, Bickers R, Morrow III G (1986) Clinical application of DNA analysis in a family with OTC deficiency. Am J Med Genet 25:513–518Google Scholar
  21. 21.
    Old JM, Purvis-Smith S, Wilcken B, Pearson P, Williamson R, Briand PL, Howard NJ, Hammond J, Cathelineau L, Davies KE (1985) Prenatal exclusion of ornithine transcarbamylase deficiency by direct gene analysis. Lancet I:73–75Google Scholar
  22. 22.
    Pembrey ME, Old JM, Leonard JV, Rodeck CH, Warren R, Davies KE (1985) Prenatal diagnosis of ornithine carbamoyl transferase deficiency using a gene specific probe. J Med Genet 22:462–465Google Scholar
  23. 23.
    Rodeck CH, Pembrey ME, Patrick AD, Tzannatos C, Whitfield AE (1982) Fetal liver biopsy for prenatal diagnosis of ornithine carbamoyl transferase deficiency. Lancet II:297–300Google Scholar
  24. 24.
    Rozen R, Fox J, Fenton WA, Horwich, AL, Rosenberg LE (1985) Gene deletion and restriction fragment length polymorphisms at the human ornithine transcarbamylase locus. Nature 313:815–817Google Scholar
  25. 25.
    Rozen R, Fox JE, Hack AM, Fenton WA, Horwich AL, Rosenberg LE (1986) DNA analysis for ornithine transcarbamylase deficiency. J Inherited Metab Dis 9 [Suppl]:49–57Google Scholar
  26. 26.
    Schmidtke J, Pape B, Krengel U, Langenbeck U, Cooper DN, Breier E, Meier H (1984) Restriction fragment length polymorphisms at the human parathyroid hormone gene locus. Hum Genet 67:428–431Google Scholar
  27. 27.
    Schwartz M, Christensen E, Christensen NC, Skovby F, Davies KE, Old JM (1986) Detection and exclusion of carriers of ornithine transcarbamylase deficiency by RFLP analysis. Clin Genet 29:449–452Google Scholar
  28. 28.
    Southern EM (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Molec Biol 98:503–517Google Scholar
  29. 29.
    Walser M (1983) Urea cycle disorders and other hereditary hyperammonemic syndromes. In: Stanbury JB, Wyngaarden JB, Frederickson DS, Goldstein JL, Brown MS (eds) The metabolic basis of inherited disease, 5th edn. McGraw-Hill, New York, pp 402–438Google Scholar
  30. 30.
    Yudkoff M, Yang W, Snodgras PJ, Segal S (1980) Ornithine transcarbamylase deficiency in a boy with normal development. J Pediatr 96:441–443Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • U. Wendel
    • 1
  • E. Wilichowski
    • 2
  • J. Schmidtke
    • 2
  • C. Bachmann
    • 3
  1. 1.Universitäts-KinderklinikDüsseldorfGermany
  2. 2.Institut für Humangenetik der UniversitätGöttingenGermany
  3. 3.Chemisches Zentrallabor, InselspitalBernSwitzerland

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