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. 2003 Aug 18;17(5):195–200. doi: 10.1002/jcla.10092

Prenatal diagnosis of Machado‐Joseph disease/spinocerebellar ataxia type 3 in Taiwan: Early detection of expanded ataxin‐3

Hui‐Fang Tsai 1,2, Chin‐San Liu 3,4, Gin‐Den Chen 5, Mei‐Ling Lin 6, Chuan Li 7, Yi‐Yun Chen 3, Bao‐Tyan Wang 8, Mingli Hsieh 7,9,10,11,✉
PMCID: PMC6808029  PMID: 12938149

Abstract

Machado‐Joseph disease (MJD)/Spinocerebellar Ataxia Type 3 (SCA3) is a rare autosomal dominative disorder in which one of the neurodegenerative disorders is caused by a translated CAG repeat expansion. Here, we present the first prenatal diagnosis of MJD in Taiwan in a woman whose husband was known to carry an unstable CAG repeat expansion in the MJD gene. After evaluating the couples' motivation and psychological tolerance, amniocentesis was performed at gestation of 13 weeks. The diagnosis was made using a simple nonradioactive polymerase chain reaction (PCR) for rapid detection of the presence of an expanded MJD allele. Meanwhile, using radioactive PCR, we identified the presence of an unusual shortness of CAG expansion in the MJD gene with 74 repeats in the fetus compared with 78 repeats in the father. After termination of the pregnancy, Western blot analysis further confirmed the presence of normal and mutant ataxin‐3 in the fetal tissue. In summary, we have performed the first prenatal diagnosis of MJD in Taiwan, and described our experience with an at‐risk male requesting counseling, carrier testing, and prenatal diagnosis for Machado‐Joseph disease. Early detection of both normal and expanded ataxin‐3 in fetal tissues was first demonstrated in the present study. J. Clin. Lab. Anal. 17: 195–200, 2003. © 2003 Wiley‐Liss, Inc.

Keywords: prenatal diagnosis, Machado‐Joseph disease, Spinocerebellar Ataxia Type 3, CAG trinucleotide repeats

REFERENCES

  • 1. Coutinho P, Calheiros JM, Andrade C. On a new degenerative disorder of the central nervous system, inherited in an autosomal dominate mode and affecting people of Azorean extraction. O Medico 1997;82:446–448. [Google Scholar]
  • 2. Rosenberg RN. Autosomal dominant cerebellar phenotypes: the genotype has settled the issue. Neurology 1995;45:1–5. [DOI] [PubMed] [Google Scholar]
  • 3. Orr HT, Chung M, Banfi S, et al. Expansion of an unstable trinucleotide CAG repeat in spinocerbellar ataxia type 1. Nat Genet 1993;4:221–226. [DOI] [PubMed] [Google Scholar]
  • 4. Sanpei K, Takano H, Igarashi S, et al. Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT. Nat Genet 1996;14:277–284. [DOI] [PubMed] [Google Scholar]
  • 5. Imbert G, Saudou F, Yvert G, et al. Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats. Nat Genet 1996;14:284–290. [DOI] [PubMed] [Google Scholar]
  • 6. Pulst SM, Nechiporuk A, Nechiporuk T, et al. Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2. Nat Genet 1996;14:269–276. [DOI] [PubMed] [Google Scholar]
  • 7. Kawaguchi Y, Okamoto T, Taniwaki M, et al. CAG expansions in a novel gene from Machado‐Joseph disease at chromosome 14q32.1. Nat Genet 1994;8:221–227. [DOI] [PubMed] [Google Scholar]
  • 8. Zhuchenko O, Bailey J, Bonnen P, et al. Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the 1A‐voltage‐dependent calcium channel. Nat Genet 1997;15:62–69. [DOI] [PubMed] [Google Scholar]
  • 9. David G, Abbas N, Stevanin G, et al. Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion. Nat Genet 1997;17:65–70. [DOI] [PubMed] [Google Scholar]
  • 10. Sutherland GR, Richards RI. Simple tandem repeats and human genetic disease. Proc Natl Acad Sci USA 1995;92:3636–3641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. Andrew SE, Goldberg YP, Kremer B, et al. The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease. Nat Genet 1993;4:398–403. [DOI] [PubMed] [Google Scholar]
  • 12. Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosome. Cell 1993;72:971–983. [DOI] [PubMed] [Google Scholar]
  • 13. Koide R, Ikeuchi T, Onodera O, et al. Unstable expansion of CAG repeat in hereditary dentatorubral‐palli‐ doluysian atrophy (DRPLA). Nat Genet 1994;6:9–13. [DOI] [PubMed] [Google Scholar]
  • 14. Nagafuchi S, Yanagisawa H, Sato K, et al. Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG trinucleotide on chromosome 12p. Nat Genet 1994;6:14–18. [DOI] [PubMed] [Google Scholar]
  • 15. La Spada AR, Wilson EM, Lubahn DB, Harding AE, Fischbeck KH. Androgen receptor gene mutations in X‐linked spinal and bulbar muscular atrophy. Nature 1991;352:77–79. [DOI] [PubMed] [Google Scholar]
  • 16. Sinden RR. Biological implication of the DNA structure associated with disease‐causing triplet repeats. Am J Hum Gene 1999;64:346–353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. Van Alfen N, Sinke RJ, Zwarts MJ, et al. Intermediate CAG repeat lengths (53, 54) for MJD/SCA3 are associated with an abnormal phenotype. Ann Neurol 2001;49:805–807. [DOI] [PubMed] [Google Scholar]
  • 18. Lopes‐Cendes I, Silveira I, Maciel P, et al. Limits of clinical assessment in the accurate diagnosis of Machado‐Joseph disease. Arch Neurol 1996;53:1168–1174. [DOI] [PubMed] [Google Scholar]
  • 19. Takiyama Y, Oyanagi S, Kawashima S, et al. A clinical and pathologic study of a large Japanese family with Machado‐Joseph disease tightly linked to the DNA markers on chromosome 14q. Neurology 1994;44:1302–1308. [DOI] [PubMed] [Google Scholar]
  • 20. Gutekunst CA, Li SH, Yi H, et al. Nuclear and neuropil aggregates in Huntington's disease: relationship to neuropathology. J Neurosci 1999;19:2522–2534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. Paulson HL, Perez MK, Trottier Y, et al. Intranuclear inclusions of expanded polyglutamine protein in spinocerebellar ataxia type 3. Neuron 1997;19:333–344. [DOI] [PubMed] [Google Scholar]
  • 22. Yamada M, Tsuji S, Takahashi H. Pathology of CAG repeat diseases. Neuropathology 2000;20:319–325. [DOI] [PubMed] [Google Scholar]
  • 23. Ko TM, Tseng LH, Hsieh FJ, Hsu PM, Lee TY. Carrier detection and prenatal diagnosis of alpha‐thalassemia of Southeast Asian deletion by polymerase chain reaction. Hum Genet 1992;88:245–248. [DOI] [PubMed] [Google Scholar]
  • 24. Wang G, Ide K, Nukina N, et al. Machado‐Joseph disease gene product identified in lymphocytes and brain. Biochem Biophys Res Comm 1997;233:476–479. [DOI] [PubMed] [Google Scholar]
  • 25. Hsieh M, Tsai HF, Lu TM, Yang CY, Wu HM, Li SY. Studies of the CAG repeat in the Machado‐Joseph disease gene in Taiwan. Hum Genet 1997;100:155–162. [DOI] [PubMed] [Google Scholar]
  • 26. Sequeiros J, Maciel P, Taborda F, et al. Prenatal diagnosis of Machado‐Joseph disease by direct mutation analysis. Prenat Diagn 1998;18:611–617. [PubMed] [Google Scholar]
  • 27. Maruyama H, Nakamura S, Matsuyama Z, et al. Molecular features of the CAG repeats and clinical manifestation of Machado‐Joseph disease. Hum Mol Genet 1995;4:807–812. [DOI] [PubMed] [Google Scholar]
  • 28. Ikeda H, Yamaguchi M, Sugai S, Aze Y, Narumiya S, Kakizuka A. Expanded polyglutamine in the Machado‐Joseph disease protein induces cell death in vitro and in vivo. Nat Genet 1996;19:196–201. [DOI] [PubMed] [Google Scholar]
  • 29. Chai Y, Koppenhafer SL, Paulson HL. Analysis of the role of heat shock protein molecular chaperones in polyglutamin disease. J Neurosci 1999;19:10338–10347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30. Maciel P, Costa MC, Ferro A, et al. Improvement in the molecular diagnosis of Machado‐Joseph disease. Arch Neurol 2001;58:1821–1827. [DOI] [PubMed] [Google Scholar]

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