Parkinsonism & related disorders

Variant R244H in Na+/Mg2+ exchanger SLC41A1 in Taiwanese Parkinson's disease is associated with loss of Mg2+ efflux function.

PMID 24661466


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. 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 293xa0cells expressing recombinant wild type and variant SLC41A1. 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. 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.