Prenatal diagnosis of Machado-Joseph disease/Spinocerebellar Ataxia Type 3 in Taiwan: early detection of expanded ataxin-3

J Clin Lab Anal. 2003;17(5):195-200. doi: 10.1002/jcla.10092.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Induced
  • Adult
  • Alleles
  • Amniocentesis
  • Ataxin-3
  • Blotting, Southern
  • Blotting, Western
  • Cells, Cultured
  • DNA / genetics
  • DNA / isolation & purification
  • Electrophoresis, Agar Gel
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Fetus
  • Fibroblasts / chemistry
  • Fibroblasts / cytology
  • Humans
  • Machado-Joseph Disease / diagnosis
  • Machado-Joseph Disease / genetics*
  • Male
  • Mutation
  • Nerve Tissue Proteins / genetics*
  • Nuclear Proteins
  • Pedigree
  • Polymerase Chain Reaction
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Repressor Proteins
  • Taiwan
  • Trinucleotide Repeat Expansion / genetics*

Substances

  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • DNA
  • ATXN3 protein, human
  • Ataxin-3