Skip to main content
PMC home page
Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 1995 Jan;32(1):25–31. doi: 10.1136/jmg.32.1.25

Machado Joseph disease maps to the same region of chromosome 14 as the spinocerebellar ataxia type 3 locus.

E C Twist 1, L K Casaubon 1, M H Ruttledge 1, V S Rao 1, P M Macleod 1, J Radvany 1, Z Zhao 1, R N Rosenberg 1, L A Farrer 1, G A Rouleau 1
PMCID: PMC1050174  PMID: 7897622

Abstract

Machado Joseph disease (MJD) is an autosomal dominantly inherited neuro-degenerative disorder primarily affecting the motor system. It can be divided into three phenotypes based on the variable combination of a range of clinical symptoms including pyramidal and extra-pyramidal features, cerebellar deficits, and distal muscle atrophy. MJD is thought to be caused by mutation of a single gene which has recently been mapped, using genetic linkage analysis, to a 29 cM region on chromosome 14q24.3-q32 in five Japanese families. A second disorder, spinocerebellar ataxia type 3 (SCA3), which has clinical symptoms similar to MJD, has also been linked to the same region of chromosome 14q in two French families. In order to narrow down the region of chromosome 14 which contains the MJD locus and to determine if this region overlaps with the predisposing locus for SCA3, we have performed genetic linkage analysis in seven MJD families, six of Portuguese/Azorean origin and one of Brazilian origin, using nine microsatellite markers mapped to 14q24.3-q32. Our results localise the MJD locus in these families to an 11 cM interval flanked by the markers D14S68 and AFM343vf1. In addition we show that this 11 cM interval maps within the 15 cM interval containing the SCA3 locus, suggesting that these diseases are allelic.

Full text

PDF

Selected References

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

  1. Barbeau A., Roy M., Cunha L., de Vincente A. N., Rosenberg R. N., Nyhan W. L., MacLeod P. L., Chazot G., Langston L. B., Dawson D. M. The natural history of Machado-Joseph disease. An analysis of 138 personally examined cases. Can J Neurol Sci. 1984 Nov;11(4 Suppl):510–525. doi: 10.1017/s0317167100034983. [DOI] [PubMed] [Google Scholar]
  2. Bharucha N. E., Bharucha E. P., Bhabha S. K. Machado-Joseph-Azorean disease in India. Arch Neurol. 1986 Feb;43(2):142–144. doi: 10.1001/archneur.1986.00520020036014. [DOI] [PubMed] [Google Scholar]
  3. Bowcock A. M., Farrer L. A., Cavalli-Sforza L. L., Hebert J. M., Kidd K. K., Frydman M., Bonne-Tamir B. Mapping the Wilson disease locus to a cluster of linked polymorphic markers on chromosome 13. Am J Hum Genet. 1987 Jul;41(1):27–35. [PMC free article] [PubMed] [Google Scholar]
  4. Braverman M. S. An algorithm to improve the computational efficiency of genetic linkage analysis. Comput Biomed Res. 1985 Feb;18(1):24–36. doi: 10.1016/0010-4809(85)90004-7. [DOI] [PubMed] [Google Scholar]
  5. Burt T., Blumbergs P., Currie B. A dominant hereditary ataxia resembling Machado-Joseph disease in Arnhem Land, Australia. Neurology. 1993 Sep;43(9):1750–1752. doi: 10.1212/wnl.43.9.1750. [DOI] [PubMed] [Google Scholar]
  6. Carson W. J., Radvany J., Farrer L. A., Vincent D., Rosenberg R. N., MacLeod P. M., Rouleau G. A. The Machado-Joseph disease locus is different from the spinocerebellar ataxia locus (SCA1). Genomics. 1992 Jul;13(3):852–855. doi: 10.1016/0888-7543(92)90168-r. [DOI] [PubMed] [Google Scholar]
  7. Cooper J. A., Nakada T., Knight R. T., Friedland R. P. Autosomal dominant motor system degeneration in a black family. Ann Neurol. 1983 Nov;14(5):585–587. doi: 10.1002/ana.410140515. [DOI] [PubMed] [Google Scholar]
  8. Coutinho P., Sequeiros J. Aspects cliniques, génétiques et pathologiques de la maladie de Machado-Joleph. J Genet Hum. 1981 Sep;29(3):203–209. [PubMed] [Google Scholar]
  9. Gyapay G., Morissette J., Vignal A., Dib C., Fizames C., Millasseau P., Marc S., Bernardi G., Lathrop M., Weissenbach J. The 1993-94 Généthon human genetic linkage map. Nat Genet. 1994 Jun;7(2 Spec No):246–339. doi: 10.1038/ng0694supp-246. [DOI] [PubMed] [Google Scholar]
  10. Harding A. E. Clinical features and classification of inherited ataxias. Adv Neurol. 1993;61:1–14. [PubMed] [Google Scholar]
  11. Jain S., Maheshwari M. C. Eight families with Joseph's disease in India. Neurology. 1990 Jan;40(1):128–131. doi: 10.1212/wnl.40.1.128. [DOI] [PubMed] [Google Scholar]
  12. Keating K. I., Dagbusan B. C. Effect of selenium deficiency on cuticle integrity in the Cladocera (Crustacea). Proc Natl Acad Sci U S A. 1984 Jun;81(11):3433–3437. doi: 10.1073/pnas.81.11.3433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kitamura J., Kubuki Y., Tsuruta K., Kurihara T., Matsukura S. A new family with Joseph disease in Japan. Homovanillic acid, magnetic resonance, and sleep apnea studies. Arch Neurol. 1989 Apr;46(4):425–428. doi: 10.1001/archneur.1989.00520400085024. [DOI] [PubMed] [Google Scholar]
  14. Koide R., Ikeuchi T., Onodera O., Tanaka H., Igarashi S., Endo K., Takahashi H., Kondo R., Ishikawa A., Hayashi T. Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA). Nat Genet. 1994 Jan;6(1):9–13. doi: 10.1038/ng0194-9. [DOI] [PubMed] [Google Scholar]
  15. Levo Y., Gorevic P. D., Kassab H. J., Zucker-Franklin D., Franklin E. C. Association between hepatitis B virus and essential mixed cryoglobulinemia. N Engl J Med. 1977 Jun 30;296(26):1501–1504. doi: 10.1056/NEJM197706302962605. [DOI] [PubMed] [Google Scholar]
  16. Livingstone I. R., Sequeiros J. Machado-Joseph disease in an American-Italian family. J Neurogenet. 1984 Apr;1(2):185–188. doi: 10.3109/01677068409107084. [DOI] [PubMed] [Google Scholar]
  17. Myers S. M., MacLeod P. M., Forse R. A., Forster-Gibson C. J., Simpson N. E. Machado-Joseph disease: linkage analysis between the loci for the disease and 18 protein markers. Cytogenet Cell Genet. 1986;43(3-4):226–228. doi: 10.1159/000132328. [DOI] [PubMed] [Google Scholar]
  18. Nagafuchi S., Yanagisawa H., Sato K., Shirayama T., Ohsaki E., Bundo M., Takeda T., Tadokoro K., Kondo I., Murayama N. Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG trinucleotide on chromosome 12p. Nat Genet. 1994 Jan;6(1):14–18. doi: 10.1038/ng0194-14. [DOI] [PubMed] [Google Scholar]
  19. Nakano K. K., Dawson D. M., Spence A. Machado disease. A hereditary ataxia in Portuguese emigrants to Massachusetts. Neurology. 1972 Jan;22(1):49–55. doi: 10.1212/wnl.22.1.49. [DOI] [PubMed] [Google Scholar]
  20. Ott J. A simple scheme for the analysis of HLA linkages in pedigrees. Ann Hum Genet. 1978 Oct;42(2):255–257. doi: 10.1111/j.1469-1809.1978.tb00657.x. [DOI] [PubMed] [Google Scholar]
  21. Ott J. Estimation of the recombination fraction in human pedigrees: efficient computation of the likelihood for human linkage studies. Am J Hum Genet. 1974 Sep;26(5):588–597. [PMC free article] [PubMed] [Google Scholar]
  22. Radvany J., Camargo C. H., Costa Z. M., Fonseca N. C., Nascimento E. D. Machado-Joseph disease of Azorean ancestry in Brazil: the Catarina kindred. Neurological, neuroimaging, psychiatric and neuropsychological findings in the largest known family, the "Catarina" kindred. Arq Neuropsiquiatr. 1993 Mar;51(1):21–30. doi: 10.1590/s0004-282x1993000100004. [DOI] [PubMed] [Google Scholar]
  23. Rosenberg R. N., Nyhan W. L., Bay C., Shore P. Autosomal dominant striatonigral degeneration. A clinical, pathologic, and biochemical study of a new genetic disorder. Neurology. 1976 Aug;26(8):703–714. doi: 10.1212/wnl.26.8.703. [DOI] [PubMed] [Google Scholar]
  24. Rosenberg R. N., Nyhan W. L., Coutinho P., Bay C. Joseph's disease: an autosomal dominant neurological disease in the Portuguese of the United States and the Azores Islands. Adv Neurol. 1978;21:33–57. [PubMed] [Google Scholar]
  25. Rouleau G. A., Wertelecki W., Haines J. L., Hobbs W. J., Trofatter J. A., Seizinger B. R., Martuza R. L., Superneau D. W., Conneally P. M., Gusella J. F. Genetic linkage of bilateral acoustic neurofibromatosis to a DNA marker on chromosome 22. Nature. 1987 Sep 17;329(6136):246–248. doi: 10.1038/329246a0. [DOI] [PubMed] [Google Scholar]
  26. Sachdev H. S., Forno L. S., Kane C. A. Joseph disease: a multisystem degenerative disorder of the nervous system. Neurology. 1982 Feb;32(2):192–195. doi: 10.1212/wnl.32.2.192. [DOI] [PubMed] [Google Scholar]
  27. Stevanin G., Le Guern E., Ravisé N., Chneiweiss H., Dürr A., Cancel G., Vignal A., Boch A. L., Ruberg M., Penet C. A third locus for autosomal dominant cerebellar ataxia type I maps to chromosome 14q24.3-qter: evidence for the existence of a fourth locus. Am J Hum Genet. 1994 Jan;54(1):11–20. [PMC free article] [PubMed] [Google Scholar]
  28. Suite N. D., Sequeiros J., McKhann G. M. Machado-Joseph disease in a Sicilian-American family. J Neurogenet. 1986 May;3(3):177–182. doi: 10.3109/01677068609106847. [DOI] [PubMed] [Google Scholar]
  29. Takiyama Y., Nishizawa M., Tanaka H., Kawashima S., Sakamoto H., Karube Y., Shimazaki H., Soutome M., Endo K., Ohta S. The gene for Machado-Joseph disease maps to human chromosome 14q. Nat Genet. 1993 Jul;4(3):300–304. doi: 10.1038/ng0793-300. [DOI] [PubMed] [Google Scholar]
  30. Twist E. C., Farrer L. A., Macleod P. M., Radvany J., Chamberlain S., Rosenberg R. N., Rouleau G. A. Machado Joseph disease is not an allele of the spinocerebellar ataxia 2 locus. Hum Genet. 1994 Mar;93(3):335–338. doi: 10.1007/BF00212034. [DOI] [PubMed] [Google Scholar]
  31. Warner T. T., Williams L., Harding A. E. DRPLA in Europe. Nat Genet. 1994 Mar;6(3):225–225. doi: 10.1038/ng0394-225a. [DOI] [PubMed] [Google Scholar]
  32. Woods B. T., Schaumburg H. H. Nigro-spino-dentatal degeneration with nuclear ophthalmoplegia. A unique and partially treatable clinico-pathological entity. J Neurol Sci. 1972 Oct;17(2):149–166. doi: 10.1016/0022-510x(72)90137-2. [DOI] [PubMed] [Google Scholar]
  33. Yakura H., Wakisaka A., Fujimoto S., Itakura K. Letter: Hereditary ataxia and HL-A. N Engl J Med. 1974 Jul 18;291(3):154–155. doi: 10.1056/NEJM197407182910314. [DOI] [PubMed] [Google Scholar]
  34. Yuasa T., Ohama E., Harayama H., Yamada M., Kawase Y., Wakabayashi M., Atsumi T., Miyatake T. Joseph's disease: clinical and pathological studies in a Japanese family. Ann Neurol. 1986 Feb;19(2):152–157. doi: 10.1002/ana.410190207. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Publishing Group

RESOURCES