The GBA-370Rec Parkinson's disease risk haplotype harbors a potentially pathogenic variant in the mitochondrial gene SLC25A44

Mol Genet Metab. 2021 May;133(1):109-112. doi: 10.1016/j.ymgme.2021.03.012. Epub 2021 Mar 18.

Abstract

GBA variations are common risk factors for Parkinson's disease (PD), and are found in 21.7% of Ashkenazi PD patients (AJ-PD), 4.23% of them carry an allele, 370Rec, which is different from the common GBA-N370S allele. Using whole-genome-sequencing of 370Rec carriers, N370S carriers, and non-carriers, we characterize the unique 370Rec haplotype in AJ-PDs, and show that it harbors a missense variant replacing the highly conserved methionine-27 with valine in the transmembrane domain of the mitochondrial SLC25A44.

Keywords: GBA; N370S; Parkinson's disease; Risk allele.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Transport Systems / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Genome, Human / genetics
  • Genotype
  • Haplotypes / genetics
  • Heterozygote
  • Humans
  • Jews / genetics
  • Male
  • Methionine / metabolism
  • Mitochondria / genetics*
  • Mitochondrial Proteins / genetics*
  • Mutation / genetics
  • Parkinson Disease / genetics*
  • Parkinson Disease / pathology
  • Risk Factors
  • Solute Carrier Proteins / genetics*
  • Whole Genome Sequencing

Substances

  • Amino Acid Transport Systems
  • Mitochondrial Proteins
  • SLC25A44 protein, human
  • Solute Carrier Proteins
  • Methionine