No Evidence for Pathogenic Role of UBQLN2 Mutations in Sporadic Amyotrophic Lateral Sclerosis in the Mainland Chinese Population

PLoS One. 2017 Jan 26;12(1):e0170943. doi: 10.1371/journal.pone.0170943. eCollection 2017.

Abstract

Mutations in the UBQLN2 gene, which encodes a member of the ubiquitin-like protein family (ubiquilin-2), have been identified in patients with dominant X-linked amyotrophic lateral sclerosis (ALS) and ALS with frontotemporal dementia (FTD). We analyzed mutations in the UBQLN2 gene in a Chinese cohort of 515 patients with sporadic ALS (sALS). A novel missense mutation (p.M392V) was detected in one sALS patient. The p.M392V mutation substitutes a highly conserved residue, has not been reported in the population databases, and previously, at the same residue, a missense mutation p.M392I was detected in two Turkey ALS patients and was considered to be pathogenic, so the M392V is a variant of uncertain significance (VOUS) for ALS. We also found a deletion mutation (p.P500_G502del), which seems to be benign. In conclusion, our data suggest that mutations in the UBQLN2 gene are rare in Chinese sALS patients.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Aged
  • Amyotrophic Lateral Sclerosis / genetics*
  • Asian People / genetics
  • Autophagy-Related Proteins
  • Cell Cycle Proteins / genetics*
  • China
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Ubiquitins / genetics*

Substances

  • Adaptor Proteins, Signal Transducing
  • Autophagy-Related Proteins
  • Cell Cycle Proteins
  • UBQLN2 protein, human
  • Ubiquitins

Grants and funding

This work was supported by the National Natural Sciences Foundation of China [81030019] (URL: http://www.nsfc.gov.cn/). No individuals employed or contracted by the funders (other than the named authors) played any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.