SLC2A1 – Childhood Absence Epilepsy

Heterozygous variants in SLC2A1 have been identified in a subset of childhood absence epilepsy patients, with five truncating or missense alleles in 50 individuals with absence epilepsy (10%) (PMID:26537434) and two variants in 26 patients with early-onset absence epilepsy (PMID:23306390), but none in 124 childhood absence epilepsy or juvenile absence cohorts (PMID:23306390). The recurrent variant c.143G>A (p.Trp48Ter) and other LoF alleles lead to haploinsufficiency of the GLUT1 transporter, impairing glucose uptake across the blood–brain barrier. Functional assays in Xenopus oocytes and patient erythrocytes have shown marked reductions in transport activity for truncating and missense mutations (PMID:10980529, PMID:11389907). However, no multigenerational segregation data are available and replication in classic childhood absence epilepsy is lacking.

References

• Epilepsia • 2015 • The role of SLC2A1 mutations in myoclonic astatic epilepsy and absence epilepsy, and the estimated frequency of GLUT1 deficiency syndrome. PMID:26537434
• Epilepsy Research • 2013 • The role of SLC2A1 in early onset and childhood absence epilepsies. PMID:23306390
• Human Mutation • 2000 • Mutational analysis of GLUT1 (SLC2A1) in Glut-1 deficiency syndrome. PMID:10980529
• FEBS Letters • 2001 • Functional consequences of the autosomal dominant G272A mutation in the human GLUT1 gene. PMID:11389907

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