Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1993 May;91(5):1884–1887. doi: 10.1172/JCI116405

Carbamyl phosphate synthetase I deficiency. One base substitution in an exon of the CPS I gene causes a 9-basepair deletion due to aberrant splicing.

R Hoshide 1, T Matsuura 1, Y Haraguchi 1, F Endo 1, M Yoshinaga 1, I Matsuda 1
PMCID: PMC288181  PMID: 8486760

Abstract

Carbamyl phosphate synthetase I (CPS I; EC6,3,4,16) is an autosomal recessive disorder characterized by hyperammonemia. We studied the molecular bases of CPS I deficiency in a newborn Japanese girl with consanguineous parents. Northern and Western blots revealed a marked decrease in CPS I mRNA and enzyme protein but with a size similar to that of the control, respectively. Sequencing of the patient's cDNA revealed a nine-nucleotide deletion at position 832-840. Sequencing analysis of the genomic DNA revealed a G to C transversion at position 840, the last nucleotide of an exon in the splice donor site. This substitution altered the consensus sequence of the splice donor site and the newly cryptical donor site in the exon caused the 9-bp in-frame deletion. This report seems to be the first complete definition of CPS I deficiency, at the molecular level.

Full text

PDF
1884

Images in this article

1885Image
on p.1885
1885Image
on p.1885
1885Image
on p.1885
1886Image
on p.1886
1886Image
on p.1886
1886Image
on p.1886
1886Image
on p.1886

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arashima S., Matsuda I. A case of carbamyl phosphate synthetase deficiency. Tohoku J Exp Med. 1972 Jun;107(2):143–147. doi: 10.1620/tjem.107.143. [DOI] [PubMed] [Google Scholar]
  2. BROWN G. W., Jr, COHEN P. P. Comparative biochemistry of urea synthesis. I. Methods for the quantitative assay of urea cycle enzymes in liver. J Biol Chem. 1959 Jul;234(7):1769–1774. [PubMed] [Google Scholar]
  3. Elliott K. R., Tipton K. F. Purification and characterisation of carbamoyl phosphate synthetase from beef liver. FEBS Lett. 1973 Nov 15;37(1):79–81. doi: 10.1016/0014-5793(73)80430-2. [DOI] [PubMed] [Google Scholar]
  4. Fearon E. R., Mallonee R. L., Phillips J. A., 3rd, O'Brien W. E., Brusilow S. W., Adcock M. W., Kirby L. T. Genetic analysis of carbamyl phosphate synthetase I deficiency. Hum Genet. 1985;70(3):207–210. doi: 10.1007/BF00273443. [DOI] [PubMed] [Google Scholar]
  5. Gelehrter T. D., Snodgrass P. J. Lethal neonatal deficiency of carbamyl phosphate synthetase. N Engl J Med. 1974 Feb 21;290(8):430–433. doi: 10.1056/NEJM197402212900804. [DOI] [PubMed] [Google Scholar]
  6. Haraguchi Y., Uchino T., Takiguchi M., Endo F., Mori M., Matsuda I. Cloning and sequence of a cDNA encoding human carbamyl phosphate synthetase I: molecular analysis of hyperammonemia. Gene. 1991 Nov 15;107(2):335–340. doi: 10.1016/0378-1119(91)90336-a. [DOI] [PubMed] [Google Scholar]
  7. Hodges P. E., Rosenberg L. E. The spfash mouse: a missense mutation in the ornithine transcarbamylase gene also causes aberrant mRNA splicing. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4142–4146. doi: 10.1073/pnas.86.11.4142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lee C. S., Curtis D., McCarron M., Love C., Gray M., Bender W., Chovnick A. Mutations affecting expression of the rosy locus in Drosophila melanogaster. Genetics. 1987 May;116(1):55–66. doi: 10.1093/genetics/116.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Mitsubuchi H., Nobukuni Y., Akaboshi I., Indo Y., Endo F., Matsuda I. Maple syrup urine disease caused by a partial deletion in the inner E2 core domain of the branched chain alpha-keto acid dehydrogenase complex due to aberrant splicing. A single base deletion at a 5'-splice donor site of an intron of the E2 gene disrupts the consensus sequence in this region. J Clin Invest. 1991 Apr;87(4):1207–1211. doi: 10.1172/JCI115120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Murotsuki J., Uehara S., Okamura K., Yajima A., Kikuchi M., Oura T., Miyabayashi S. [Prenatal diagnosis of carbamyl phosphate synthetase deficiency by fetal liver biopsy]. Nihon Sanka Fujinka Gakkai Zasshi. 1991 Dec;43(12):1613–1616. [PubMed] [Google Scholar]
  11. Nagata N., Matsuda I., Oyanagi K. Estimated frequency of urea cycle enzymopathies in Japan. Am J Med Genet. 1991 May 1;39(2):228–229. doi: 10.1002/ajmg.1320390226. [DOI] [PubMed] [Google Scholar]
  12. Piceni Sereni L., Bachmann C., Pfister U., Buscaglia M., Nicolini U. Prenatal diagnosis of carbamoyl-phosphate synthetase deficiency by fetal liver biopsy. Prenat Diagn. 1988 May;8(4):307–309. doi: 10.1002/pd.1970080411. [DOI] [PubMed] [Google Scholar]
  13. Pierson D. L., Brien J. M. Human carbamylphosphate synthetase I. Stabilization, purification, and partial characterization of the enzyme from human liver. J Biol Chem. 1980 Aug 25;255(16):7891–7895. [PubMed] [Google Scholar]
  14. Pierson D. L., Brien J. M. Human carbamylphosphate synthetase I. Stabilization, purification, and partial characterization of the enzyme from human liver. J Biol Chem. 1980 Aug 25;255(16):7891–7895. [PubMed] [Google Scholar]
  15. RUSSELL A., LEVIN B., OBERHOLZER V. G., SINCLAIR L. Hyperammonaemia. A new instance of an inborn enzymatic defect of the biosynthesis of urea. Lancet. 1962 Oct 6;2(7258):699–700. doi: 10.1016/s0140-6736(62)90508-1. [DOI] [PubMed] [Google Scholar]
  16. Raijman L., Jones M. E. Purification, composition, and some properties of rat liver carbamyl phosphate synthetase (ammonia). Arch Biochem Biophys. 1976 Jul;175(1):270–278. doi: 10.1016/0003-9861(76)90508-7. [DOI] [PubMed] [Google Scholar]
  17. Ryall J., Nguyen M., Bendayan M., Shore G. C. Expression of nuclear genes encoding the urea cycle enzymes, carbamoyl-phosphate synthetase I and ornithine carbamoyl transferase, in rat liver and intestinal mucosa. Eur J Biochem. 1985 Oct 15;152(2):287–292. doi: 10.1111/j.1432-1033.1985.tb09196.x. [DOI] [PubMed] [Google Scholar]
  18. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  19. Shapiro M. B., Senapathy P. RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression. Nucleic Acids Res. 1987 Sep 11;15(17):7155–7174. doi: 10.1093/nar/15.17.7155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Vidaud M., Gattoni R., Stevenin J., Vidaud D., Amselem S., Chibani J., Rosa J., Goossens M. A 5' splice-region G----C mutation in exon 1 of the human beta-globin gene inhibits pre-mRNA splicing: a mechanism for beta+-thalassemia. Proc Natl Acad Sci U S A. 1989 Feb;86(3):1041–1045. doi: 10.1073/pnas.86.3.1041. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES