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

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.