Frequency of Parkinson's Disease Genes and Role of PARK2 in Amyotrophic Lateral Sclerosis: An NGS Study

Genes (Basel). 2022 Jul 22;13(8):1306. doi: 10.3390/genes13081306.

Abstract

Amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) patients show a higher prevalence of Lewy body disease than the general population. Additionally, parkinsonian features were found in about 30% of ALS patients. We aimed to explore the frequency of Parkinson's disease (PD)-causative genes in ALS patients, compared to AD and healthy controls (HCs). We used next-generation sequencing multigene panels by analyzing SNCA, LRRK2, PINK1, PARK2, PARK7, SYNJ1, CHCHD2, PLA2G6, GCH1, ATP13A2, DNAJC6 and FBXO genes. GBA gene, a risk factor for PD, was also analyzed. In total, 130 ALS and 100 AD patients were investigated. PD-related genes were found to be altered in 26.2% of ALS, 20% of AD patients and 19.2% of HCs. Autosomal recessive genes were significantly more involved in ALS as compared to AD and HCs (p = 0.021). PARK2 variants were more frequent in ALS than in AD and HCs, although not significantly. However, the p.Arg402Cys variant was increased in ALS than in HCs (p = 0.025). This finding is consistent with current literature, as parkin levels were found to be decreased in ALS animal models and patients. Our results confirm the possible role of PD-related genes as risk modifier in ALS pathogenesis.

Keywords: Alzheimer’s disease; GBA; PD-related genes; Parkinson’s disease; amyotrophic lateral sclerosis; neurodegenerative diseases.

MeSH terms

  • Alzheimer Disease* / genetics
  • Amyotrophic Lateral Sclerosis* / genetics
  • Genetic Predisposition to Disease
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Parkinson Disease* / genetics
  • Ubiquitin-Protein Ligases* / genetics

Substances

  • Ubiquitin-Protein Ligases
  • parkin protein

Grants and funding

This research received no external funding.