Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

A donor splice site mutation in the parathyroid hormone gene is associated with autosomal recessive hypoparathyroidism

Abstract

Investigation of one kindred with autosomal recessive isolated hypoparathyroidism, which had resulted from a consanguineous marriage, has identified a g to c substitution in the first nucleotide of intron 2 of the parathyroid hormone (PTH) gene. This donor splice mutation could be detected by restriction enzyme cleavage with DdeI, and this revealed that the patients were homozygous for the mutant alleles, the unaffected relatives were heterozygous, and unrelated normals were homozygous for the wild type alleles. Defects in messenger RNA splicing were investigated by the detection of illegitimate transcription of the PTH gene in lymphoblastoid cells. The mutation resulted in exon skipping with a loss of exon 2, which encodes the initiation codon and the signal peptide, thereby causing parathyroid hormone deficiency.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. McKusick, V.A. Mendelian Inheritance in Man (Johns Hopkins University Press, Baltimore, 1988).

    Google Scholar 

  2. Barr, D.G.D., Prader, A., Esper, U., Rampini, S., Marrian, V.J. & Forfar, J.O. Helv. Paediatr. Acta 26, 507–521 (1971).

    CAS  PubMed  Google Scholar 

  3. Bronsky, D., Kiamlko, R.T. & Waldstein, S.S. J. clin. Endocrinol. Metabol. 28, 61–65 (1968).

    Article  CAS  Google Scholar 

  4. Whyte, M.P. & Weldon, V.V. J. Pediatr. 99, 608–611 (1981).

    Article  CAS  Google Scholar 

  5. Keutmann, H.T., Sauer, M.M., Hendy, G.N., O'Riordan, J.L.H. & Potts, J.T., Jr. Biochemistry 12, 5723–5729 (1978).

    Article  Google Scholar 

  6. Naylor, S.L. et al. Som. Cell Genet. 9, 609–616 (1983).

    Article  CAS  Google Scholar 

  7. Ahn, T.G., Antonarakis, S.E., Kronenberg, H.M., Igarashi, T. & Levine, M.A. Medicine 65, 73–81 (1986).

    Article  CAS  Google Scholar 

  8. Thakker, R.V., Davies, K.E., Whyte, M.P., Wooding, C. & O'Riordan, J.L.H. J. clin. Invest. 86, 40–45 (1990).

    Article  CAS  Google Scholar 

  9. Arnold, A., Horst, S.A., Gardella, T.J., Baba, H., Levine, M.A. & Kronenberg, H.M. J. clin. Invest. 86, 1084–1087 (1990).

    Article  CAS  Google Scholar 

  10. Chelly, J., Concordet, J-P., Kaplan, J-C. & Kahn, A. Proc. natn. Acad. Sci. U.S.A. 86, 2617–2621 (1989).

    Article  CAS  Google Scholar 

  11. Sarkar, G. & Sommer, S.S. Science 244, 331–334 (1989).

    Article  CAS  Google Scholar 

  12. Chelly, J., Kaplan, J.-C., Maire, P., Gautron, S. & Kahn, A. Nature 333, 858–860 (1988).

    Article  CAS  Google Scholar 

  13. Berg, L-P. et al. Hum. Genet. 85, 655–658 (1990).

    Article  CAS  Google Scholar 

  14. Schmidtke, J. et al. Hum. Genet. 67, 428–431 (1984).

    Article  CAS  Google Scholar 

  15. Vasicek, T.J. et al. Proc. natn. Acad. Sci. U.S.A. 80, 2127–2131 (1983).

    Article  CAS  Google Scholar 

  16. Breathnach, R., Benoist, C., O'Hare, K., Gannon, F. & Chambon, P. Proc. natn. Acad. Sci. U.S.A. 75, 4853–4857 (1978).

    Article  CAS  Google Scholar 

  17. Kozak, M. J. cell Biol. 108, 229–241 (1989).

    Article  CAS  Google Scholar 

  18. Emr, S.D., Hall, M.N. & Silhavy, T.J. J. cell Biol. 86, 701–711 (1980).

    Article  CAS  Google Scholar 

  19. Treisman, R., Orkin, S.H. & Maniatis, T. Nature 302, 591–596 (1983).

    Article  CAS  Google Scholar 

  20. Ohno, K. & Suzuki, K. J. biol. Chem. 263, 18563–18567 (1988).

    CAS  PubMed  Google Scholar 

  21. Nicholls, A.C., Oliver, J., Renouf, D.V., McPheat, J., Palan, A. & Pope, F.M. Hum. Genet. 87, 193–198 (1991).

    Article  CAS  Google Scholar 

  22. Talerico, M. & Berget, S.M. Molec. Cell Biol. 10, 6299–6305 (1990).

    Article  CAS  Google Scholar 

  23. Kuo, H-C., Nasim, F-U.H. & Grabowski, P.J. Science 251, 1045–1050 (1991).

    Article  CAS  Google Scholar 

  24. Nussbaum, S.R. et al. Clin. Chem. 33, 1364–1367 (1987).

    CAS  PubMed  Google Scholar 

  25. Roelen, D.L., Frolich, M. & Papapoulos, S.E. Eur. J. clin. Invest. 19, 311–315 (1989).

    Article  CAS  Google Scholar 

  26. Saiki, R.K. et al. Science 239, 487–491 (1988).

    Article  CAS  Google Scholar 

  27. Bachman, B., Kuke, W. & Hunsmann, G. Nucl. Acid. Res. 18, 1309 (1990).

    Article  Google Scholar 

  28. Lovell-Badge, R.H. In Teratocarcinomas and Embyronic Stem Cells, a Practical Approach (ed. Robertson, E. J.) 153–182 (Oxford IRL Press, 1987).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Parkinson, D., Thakker, R. A donor splice site mutation in the parathyroid hormone gene is associated with autosomal recessive hypoparathyroidism. Nat Genet 1, 149–152 (1992). https://doi.org/10.1038/ng0592-149

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0592-149

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing