Skip to main content
NCBI home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1993 Jul;53(1):125–130.

The normal Huntington disease (HD) allele, or a closely linked gene, influences age at onset of HD.

L A Farrer 1, L A Cupples 1, P Wiater 1, P M Conneally 1, J F Gusella 1, R H Myers 1
PMCID: PMC1682222  PMID: 8317477

Abstract

We evaluated the hypothesis that Huntington disease (HD) is influenced by the normal HD allele by comparing transmission patterns of genetically linked markers at the D4S10 locus in the normal parent against age at onset in the affected offspring. Analysis of information from 21 sibships in 14 kindreds showed a significant tendency for sibs who have similar onset ages to share the same D4S10 allele from the normal parent. Affected sibs who inherited different D4S10 alleles from the normal parent tended to have more variable ages at onset. These findings suggest that the expression of HD is modulated by the normal HD allele or by a closely linked locus.

Full text

PDF
125

Selected References

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

  1. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell. 1993 Mar 26;72(6):971–983. doi: 10.1016/0092-8674(93)90585-e. [DOI] [PubMed] [Google Scholar]
  2. Baker H. E., Poulter M., Crow T. J., Frith C. D., Lofthouse R., Ridley R. M. Aminoacid polymorphism in human prion protein and age at death in inherited prion disease. Lancet. 1991 May 25;337(8752):1286–1286. doi: 10.1016/0140-6736(91)92953-y. [DOI] [PubMed] [Google Scholar]
  3. Boehnke M., Conneally P. M., Lange K. Two models for a maternal factor in the inheritance of Huntington disease. Am J Hum Genet. 1983 Sep;35(5):845–860. [PMC free article] [PubMed] [Google Scholar]
  4. Collinge J., Harding A. E., Owen F., Poulter M., Lofthouse R., Boughey A. M., Shah T., Crow T. J. Diagnosis of Gerstmann-Sträussler syndrome in familial dementia with prion protein gene analysis. Lancet. 1989 Jul 1;2(8653):15–17. doi: 10.1016/s0140-6736(89)90256-0. [DOI] [PubMed] [Google Scholar]
  5. Conneally P. M., Haines J. L., Tanzi R. E., Wexler N. S., Penchaszadeh G. K., Harper P. S., Folstein S. E., Cassiman J. J., Myers R. H., Young A. B. Huntington disease: no evidence for locus heterogeneity. Genomics. 1989 Aug;5(2):304–308. doi: 10.1016/0888-7543(89)90062-1. [DOI] [PubMed] [Google Scholar]
  6. Conneally P. M. Huntington disease: genetics and epidemiology. Am J Hum Genet. 1984 May;36(3):506–526. [PMC free article] [PubMed] [Google Scholar]
  7. Erickson R. P. Chromosomal imprinting and the parent transmission specific variation in expressivity of Huntington disease. Am J Hum Genet. 1985 Jul;37(4):827–829. [PMC free article] [PubMed] [Google Scholar]
  8. Farrer L. A., Conneally P. M. A genetic model for age at onset in Huntington disease. Am J Hum Genet. 1985 Mar;37(2):350–357. [PMC free article] [PubMed] [Google Scholar]
  9. Farrer L. A., Conneally P. M., Yu P. L. The natural history of Huntington disease: possible role of "aging genes". Am J Med Genet. 1984 May;18(1):115–123. doi: 10.1002/ajmg.1320180115. [DOI] [PubMed] [Google Scholar]
  10. Farrer L. A., Cupples L. A., Kiely D. K., Conneally P. M., Myers R. H. Inverse relationship between age at onset of Huntington disease and paternal age suggests involvement of genetic imprinting. Am J Hum Genet. 1992 Mar;50(3):528–535. [PMC free article] [PubMed] [Google Scholar]
  11. Farrer L. A., Florio L. P., Bruce M. L., Leaf P. J., Weissman M. M. Reliability of self-reported age at onset of major depression. J Psychiatr Res. 1989;23(1):35–47. doi: 10.1016/0022-3956(89)90015-0. [DOI] [PubMed] [Google Scholar]
  12. Faught E., Falgout J. C., Leli D. A. Late-onset variant of Huntington's chorea. South Med J. 1983 Oct;76(10):1266–1270. doi: 10.1097/00007611-198310000-00018. [DOI] [PubMed] [Google Scholar]
  13. Gilliam T. C., Tanzi R. E., Haines J. L., Bonner T. I., Faryniarz A. G., Hobbs W. J., MacDonald M. E., Cheng S. V., Folstein S. E., Conneally P. M. Localization of the Huntington's disease gene to a small segment of chromosome 4 flanked by D4S10 and the telomere. Cell. 1987 Aug 14;50(4):565–571. doi: 10.1016/0092-8674(87)90029-8. [DOI] [PubMed] [Google Scholar]
  14. Gusella J. F., Wexler N. S., Conneally P. M., Naylor S. L., Anderson M. A., Tanzi R. E., Watkins P. C., Ottina K., Wallace M. R., Sakaguchi A. Y. A polymorphic DNA marker genetically linked to Huntington's disease. Nature. 1983 Nov 17;306(5940):234–238. doi: 10.1038/306234a0. [DOI] [PubMed] [Google Scholar]
  15. Hall J. G., Te-Juatco L. Association between age of onset and parental inheritance in Huntington chorea. Am J Med Genet. 1983 Oct;16(2):289–290. doi: 10.1002/ajmg.1320160218. [DOI] [PubMed] [Google Scholar]
  16. Myers R. H., Cupples L. A., Schoenfeld M., D'Agostino R. B., Terrin N. C., Goldmakher N., Wolf P. A. Maternal factors in onset of Huntington disease. Am J Hum Genet. 1985 May;37(3):511–523. [PMC free article] [PubMed] [Google Scholar]
  17. Myers R. H., Goldman D., Bird E. D., Sax D. S., Merril C. R., Schoenfeld M., Wolf P. A. Maternal transmission in Huntington's disease. Lancet. 1983 Jan 29;1(8318):208–210. doi: 10.1016/s0140-6736(83)92587-4. [DOI] [PubMed] [Google Scholar]
  18. Myers R. H., Madden J. J., Teague J. L., Falek A. Factors related to onset age of Huntington disease. Am J Hum Genet. 1982 May;34(3):481–488. [PMC free article] [PubMed] [Google Scholar]
  19. Myers R. H., Sax D. S., Koroshetz W. J., Mastromauro C., Cupples L. A., Kiely D. K., Pettengill F. K., Bird E. D. Factors associated with slow progression in Huntington's disease. Arch Neurol. 1991 Aug;48(8):800–804. doi: 10.1001/archneur.1991.00530200036015. [DOI] [PubMed] [Google Scholar]
  20. Myers R. H., Sax D. S., Schoenfeld M., Bird E. D., Wolf P. A., Vonsattel J. P., White R. F., Martin J. B. Late onset of Huntington's disease. J Neurol Neurosurg Psychiatry. 1985 Jun;48(6):530–534. doi: 10.1136/jnnp.48.6.530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Newcombe R. G., Walker D. A., Harper P. S. Factors influencing age at onset and duration of survival in Huntington's chorea. Ann Hum Genet. 1981 Oct;45(Pt 4):387–396. doi: 10.1111/j.1469-1809.1981.tb00352.x. [DOI] [PubMed] [Google Scholar]
  22. Pericak-Vance M. A., Elston R. C., Conneally P. M., Dawson D. V. Age-of-onset heterogeneity in Huntington disease families. Am J Med Genet. 1983 Jan;14(1):49–59. doi: 10.1002/ajmg.1320140109. [DOI] [PubMed] [Google Scholar]
  23. Reik W. Genomic imprinting: a possible mechanism for the parental origin effect in Huntington's chorea. J Med Genet. 1988 Dec;25(12):805–808. doi: 10.1136/jmg.25.12.805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ridley R. M., Farrer L. A., Frith C. D., Conneally P. M. A test of the hypothesis that age at onset in Huntington disease is controlled by an X-linked recessive modifier. Am J Hum Genet. 1992 Mar;50(3):536–543. [PMC free article] [PubMed] [Google Scholar]
  25. Ridley R. M., Frith C. D., Crow T. J., Conneally P. M. Anticipation in Huntington's disease is inherited through the male line but may originate in the female. J Med Genet. 1988 Sep;25(9):589–595. doi: 10.1136/jmg.25.9.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ridley R. M., Frith C. D., Farrer L. A., Conneally P. M. Patterns of inheritance of the symptoms of Huntington's disease suggestive of an effect of genomic imprinting. J Med Genet. 1991 Apr;28(4):224–231. doi: 10.1136/jmg.28.4.224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sax D. S., Bird E. D., Gusella J. F., Myers R. H. Phenotypic variation in 2 Huntington's disease families with linkage to chromosome 4. Neurology. 1989 Oct;39(10):1332–1336. doi: 10.1212/wnl.39.10.1332. [DOI] [PubMed] [Google Scholar]
  28. Silverman J. M., Breitner J. C., Mohs R. C., Davis K. L. Reliability of the family history method in genetic studies of Alzheimer's disease and related dementias. Am J Psychiatry. 1986 Oct;143(10):1279–1282. doi: 10.1176/ajp.143.10.1279. [DOI] [PubMed] [Google Scholar]
  29. Vonsattel J. P., Myers R. H., Stevens T. J., Ferrante R. J., Bird E. D., Richardson E. P., Jr Neuropathological classification of Huntington's disease. J Neuropathol Exp Neurol. 1985 Nov;44(6):559–577. doi: 10.1097/00005072-198511000-00003. [DOI] [PubMed] [Google Scholar]
  30. Wallace D. C., Hall A. C. Evidence of genetic heterogeneity in Huntington's chorea. J Neurol Neurosurg Psychiatry. 1972 Dec;35(6):789–800. doi: 10.1136/jnnp.35.6.789. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES