Factors Associated with Intergenerational Instability of ATXN3 CAG Repeat and Genetic Anticipation in Chinese Patients with Spinocerebellar Ataxia Type 3

Cerebellum. 2020 Dec;19(6):902-906. doi: 10.1007/s12311-020-01167-x.

Abstract

Spinocerebellar ataxia type 3 (SCA3) is caused by unstable expanded CAG repeats (expCAGs) in ATXN3. Factors associated with intergenerational instability (delta-expCAG) and genetic anticipation in SCA3 have never been reported in Chinese mainland. Here, we demonstrated that unstable transmissions occurred more often in sons than in daughters (91% vs 72%, Fisher's exact test, p = 0.012). The extended delta-expCAG of father-son transmissions was greater than that of mother-son transmissions (3.8 ± 2.3 repeats vs 1.6 ± 1.0 repeats, Mann-Whitney U, p = 0.001). Genetic anticipation was frequently observed between generations but not affected by the delta-expCAG.

Keywords: Chinese; Genetic anticipation; Intergenerational transmission; Spinocerebellar ataxia type 3.

MeSH terms

  • Adult
  • Anticipation, Genetic / genetics*
  • Asian People / genetics*
  • Ataxin-3 / genetics*
  • China / epidemiology
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Machado-Joseph Disease / diagnosis
  • Machado-Joseph Disease / epidemiology*
  • Machado-Joseph Disease / genetics*
  • Male
  • Middle Aged
  • Repressor Proteins / genetics*
  • Trinucleotide Repeat Expansion / genetics*
  • Trinucleotide Repeats / genetics
  • Young Adult

Substances

  • Repressor Proteins
  • ATXN3 protein, human
  • Ataxin-3