title: Variant R244H in Na+/Mg2+ exchanger SLC41A1 in Taiwanese Parkinson's disease is associated with loss of Mg2+ efflux function.
abstract: BACKGROUND
  Sequence variants in SLC41A1 have been reported to be associated with Parkinson's disease (PD). This study investigates whether the genetic variants in SLC41A1 contribute to Taiwanese PD.
  
  
  METHODS
  We sequenced SLC41A1 cDNA fragments from 80 patients with early onset PD. A cohort of PD and ethnically matched controls were examined for the sequence variant. The effect of variation on Mg(2+) homeostasis was further examined using stably induced 293 cells expressing recombinant wild type and variant SLC41A1.
  
  
  RESULTS
  A novel heterozygous R244H in the SLC41A1 gene was identified in one early onset PD patient, which not present either in 479 PD patients or 525 normal controls with age onset >50. Both wild type and R244H SLC41A1-V5-His proteins were co-localized to areas of the plasma membrane that were stained using wheat germ agglutinin (WGA). Fluorescent probe mag-fluo-4 staining indicated that R244H SLC41A1 is dysfunctional in Mg(2+) efflux.
  
  
  CONCLUSIONS
  This study has shown loss of Mg(2+) efflux function consequent to SLC41A1 R244H variant and SLC41A1 coding variants seem to be rare in Taiwanese PD.
authors.affiliation: Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 199 Tung-Hwa North Road, Taipei 10507, Taiwan.
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 199 Tung-Hwa North Road, Taipei 10507, Taiwan.
authors.forename: Yih-Ru
authors.initials: YR
authors.lastname: Wu
authors.affiliation: Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 199 Tung-Hwa North Road, Taipei 10507, Taiwan.
authors.forename: Wan-Ling
authors.initials: WL
authors.lastname: Chen
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Hao-Chun
authors.initials: HC
authors.lastname: Wang
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Chi-Mei
authors.initials: CM
authors.lastname: Lee
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan. Electronic address: t43019@ntnu.edu.tw.
authors.forename: Guey-Jen
authors.initials: GJ
authors.lastname: Lee-Chen
authors.affiliation: Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 199 Tung-Hwa North Road, Taipei 10507, Taiwan. Electronic address: cmchen@adm.cgmh.org.tw.
authors.forename: Chiung-Mei
authors.initials: CM
authors.lastname: Chen
mesh_terms: D000328:Adult; D001120:Arginine / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D057809:HEK293 Cells; D006639:Histidine / Q000235:genetics*; D006801:Humans; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D010300:Parkinson Disease / Q000235:genetics*; D013624:Taiwan; D014162:Transfection
chemical_list: D027682:Cation Transport Proteins; C476304:SLC41A1 protein, human; D006639:Histidine; D001120:Arginine; D008274:Magnesium
keywords: Mg(2+) homeostasis; Mutation screen; Parkinson's disease; Solute carrier family 41 member 1 (SLC41A1)