Analysis of the GGGGCC Repeat Expansions of the C9orf72 Gene in SCA3/MJD Patients from China

PLoS One. 2015 Jun 17;10(6):e0130336. doi: 10.1371/journal.pone.0130336. eCollection 2015.

Abstract

Neurodegenerative disorders are a heterogeneous group of chronic progressive diseases and have pathological mechanisms in common. A certain causative gene identified for a particular disease may be found to play roles in more than one neurodegenerative disorder. We analyzed the GGGGCC repeat expansions of C9orf72 gene in patients with SCA3/MJD from mainland China to determine whether the C9orf72 gene plays a role in the pathogenesis of SCA3/MJD. In our study, there were no pathogenic repeats (>30 repeats) detected in either the patients or controls. SCA3/MJD patients with intermediate/intermediate or short/intermediate genotype (short: <7 repeats; intermediate: 7-30 repeats) of the GGGGCC repeats had an earlier onset compared with those with short/short genotype. The presence of the intermediate allele of the GGGGCC repeats in the patients decreased the age at onset by nearly 3 years. Our study firstly demonstrate that the development of SCA3/MJD may involve some physiological functions of the C9orf72 gene and provide new evidence to the hypothesis that a specific mutation identified in one of the neurodegenerative disorders may be a modulator in this class of diseases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • C9orf72 Protein
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Genotype
  • Humans
  • Machado-Joseph Disease / genetics*
  • Male
  • Polymerase Chain Reaction
  • Prognosis
  • Proteins / genetics*
  • Trinucleotide Repeat Expansion / genetics*

Substances

  • C9orf72 Protein
  • C9orf72 protein, human
  • Proteins

Grants and funding

This study was supported by the National Basic Research Program (973 Program) (Nos. 2012CB944601, 2012CB517902 and 2011CB510002 to Hong Jiang), the New Century Excellent Talents in University (No. NCET-10-0836 to Hong Jiang), the National Natural Science Foundation of China (Nos. 81410308019, 81471156, 81271260, 30971585 to Hong Jiang), Hunan Funds for Distinguished Young Scientists (No. 14JJ1008 to Hong Jiang), Xinjiang Natural Science Foundation (No. 201318101-4 to Hong Jiang), the Undergraduate Innovation Project of Central South University (No. YB13028, 201410533324 to Hong Jiang), Fundamental Research Funds for the Central Universities of Central South University (No. 2014zzts078 to Zhao Chen) and High-level medical personnel of Hunan province 225 Project.