Skip to main content
NCBI home page
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1998 Sep;57(9):524–526. doi: 10.1136/ard.57.9.524

Evidence for genetic anticipation in nodal osteoarthritis

G Wright 1, M Regan 1, C Deighton 1, G Wallis 1, M Doherty 1
PMCID: PMC1752739  PMID: 9849310

Abstract

OBJECTIVE—Evidence was sought for genetic anticipation (disease occurring at an earlier age in subsequent generations, with increasing severity) in nodal osteoarthritis (NOA).
METHODS—Age at symptom onset and disease severity was compared within 30 parent/offspring pairs with NOA. Correlation between the offspring age of disease onset and the parental age at conception was also assessed.
RESULTS—The age at onset of nodal symptoms was earlier in the offspring (43 years (95% confidence intervals (CI) 38 to 47) v 61 (CI 58 to 65); mean difference 18 years (CI 13 to 22): p< 0.001) as was large joint symptom onset (48 years (CI 41 to 55) v 67 (CI 61 to 73); mean difference 20 years (CI 13 to 27): p< 0.01). A negative correlation existed between age of offspring symptom onset and parental age at conception. Fifteen (50%) offspring had similar or more extensive disease than their parents.
CONCLUSIONS—These results suggest genetic anticipation occurs in NOA and if confirmed a search for trinucleotide repeats is warranted.

 Keywords: nodal osteoarthritis; genetic anticipation; trinucleotide repeats

Full Text

The Full Text of this article is available as a PDF (96.6 KB).

Selected References

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

  1. Adams P., Falek A., Arnold J. Huntington disease in Georgia: age at onset. Am J Hum Genet. 1988 Nov;43(5):695–704. [PMC free article] [PubMed] [Google Scholar]
  2. Bassett A. S., Honer W. G. Evidence for anticipation in schizophrenia. Am J Hum Genet. 1994 May;54(5):864–870. [PMC free article] [PubMed] [Google Scholar]
  3. Brook J. D., McCurrach M. E., Harley H. G., Buckler A. J., Church D., Aburatani H., Hunter K., Stanton V. P., Thirion J. P., Hudson T. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member. Cell. 1992 Feb 21;68(4):799–808. doi: 10.1016/0092-8674(92)90154-5. [DOI] [PubMed] [Google Scholar]
  4. Buxton J., Shelbourne P., Davies J., Jones C., Van Tongeren T., Aslanidis C., de Jong P., Jansen G., Anvret M., Riley B. Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy. Nature. 1992 Feb 6;355(6360):547–548. doi: 10.1038/355547a0. [DOI] [PubMed] [Google Scholar]
  5. Deighton C., Heslop P., McDonagh J., Walker D., Thomson G. Does genetic anticipation occur in familial rheumatoid arthritis? Ann Rheum Dis. 1994 Dec;53(12):833–835. doi: 10.1136/ard.53.12.833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gregersen P. K. Discordance for autoimmunity in monozygotic twins. Are "identical" twins really identical? Arthritis Rheum. 1993 Sep;36(9):1185–1192. doi: 10.1002/art.1780360902. [DOI] [PubMed] [Google Scholar]
  7. Harley H. G., Brook J. D., Rundle S. A., Crow S., Reardon W., Buckler A. J., Harper P. S., Housman D. E., Shaw D. J. Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy. Nature. 1992 Feb 6;355(6360):545–546. doi: 10.1038/355545a0. [DOI] [PubMed] [Google Scholar]
  8. Harley H. G., Brook J. D., Rundle S. A., Crow S., Reardon W., Buckler A. J., Harper P. S., Housman D. E., Shaw D. J. Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy. Nature. 1992 Feb 6;355(6360):545–546. doi: 10.1038/355545a0. [DOI] [PubMed] [Google Scholar]
  9. Harley H. G., Rundle S. A., MacMillan J. C., Myring J., Brook J. D., Crow S., Reardon W., Fenton I., Shaw D. J., Harper P. S. Size of the unstable CTG repeat sequence in relation to phenotype and parental transmission in myotonic dystrophy. Am J Hum Genet. 1993 Jun;52(6):1164–1174. [PMC free article] [PubMed] [Google Scholar]
  10. Harper P. S., Harley H. G., Reardon W., Shaw D. J. Anticipation in myotonic dystrophy: new light on an old problem. Am J Hum Genet. 1992 Jul;51(1):10–16. [PMC free article] [PubMed] [Google Scholar]
  11. KELLGREN J. H., LAWRENCE J. S., BIER F. GENETIC FACTORS IN GENERALIZED OSTEO-ARTHROSIS. Ann Rheum Dis. 1963 Jul;22:237–255. doi: 10.1136/ard.22.4.237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Maddox J. Triplet repeat genes raise questions. Nature. 1994 Apr 21;368(6473):685–685. doi: 10.1038/368685a0. [DOI] [PubMed] [Google Scholar]
  13. McConkie-Rosell A., Lachiewicz A. M., Spiridigliozzi G. A., Tarleton J., Schoenwald S., Phelan M. C., Goonewardena P., Ding X., Brown W. T. Evidence that methylation of the FMR-I locus is responsible for variable phenotypic expression of the fragile X syndrome. Am J Hum Genet. 1993 Oct;53(4):800–809. [PMC free article] [PubMed] [Google Scholar]
  14. McInnis M. G., McMahon F. J., Chase G. A., Simpson S. G., Ross C. A., DePaulo J. R., Jr Anticipation in bipolar affective disorder. Am J Hum Genet. 1993 Aug;53(2):385–390. [PMC free article] [PubMed] [Google Scholar]
  15. Polito J. M., 2nd, Rees R. C., Childs B., Mendeloff A. I., Harris M. L., Bayless T. M. Preliminary evidence for genetic anticipation in Crohn's disease. Lancet. 1996 Mar 23;347(9004):798–800. doi: 10.1016/s0140-6736(96)90870-3. [DOI] [PubMed] [Google Scholar]
  16. Spector T. D., Cicuttini F., Baker J., Loughlin J., Hart D. Genetic influences on osteoarthritis in women: a twin study. BMJ. 1996 Apr 13;312(7036):940–943. doi: 10.1136/bmj.312.7036.940. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Stecher R. M., Hersh A. H. HEBERDEN'S NODES: THE MECHANISM OF INHERITANCE IN HYPERTROPHIC ARTHRITIS OF THE FINGERS. J Clin Invest. 1944 Sep;23(5):699–704. doi: 10.1172/JCI101540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Verkerk A. J., Pieretti M., Sutcliffe J. S., Fu Y. H., Kuhl D. P., Pizzuti A., Reiner O., Richards S., Victoria M. F., Zhang F. P. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell. 1991 May 31;65(5):905–914. doi: 10.1016/0092-8674(91)90397-h. [DOI] [PubMed] [Google Scholar]
  19. Wright G. D., Hughes A. E., Regan M., Doherty M. Association of two loci on chromosome 2q with nodal osteoarthritis. Ann Rheum Dis. 1996 May;55(5):317–319. doi: 10.1136/ard.55.5.317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Zheng C. J., Byers B., Moolgavkar S. H. Allelic instability in mitosis: a unified model for dominant disorders. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10178–10182. doi: 10.1073/pnas.90.21.10178. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group

RESOURCES