Uncovering microdeletions in patients with severe Glut-1 deficiency syndrome using SNP oligonucleotide microarray analysis

Glut-1 facilitates the diffusion of glucose across the blood–brain barrier and is responsible for glucose entry into the brain. Impaired glucose transport across the blood–brain barrier results in Glut-1 deficiency syndrome (Glut-1 DS, OMIM 606777), characterized in its most severe form by infantile seizures, developmental delay, acquired microcephaly, spasticity, ataxia, and hypoglycorrhachia. Approximately 93% of patients with Glut-1 DS have identifiable mutations by sequence analysis in SLC2A1 which localizes to chromosome 1p34.2. In this report, we describe seven severe cases of Glut-1 DS, including a set of identical twins, caused by microdeletions in the SLC2A1 region. These patients were all mutation negative by molecular sequencing. Microdeletions ranged in size from 45 Kb to 4.51 Mb, and all were identified using high resolution single nucleotide polymorphism (SNP) oligonucleotide microarray analysis (SOMA). Cases with microdeletions ⩽82 Kb were not resolvable by FISH. All patients had severe epilepsy, significant cognitive and motor delay, ataxia, and microcephaly. MRI changes, when present, were of greater severity than are typically associated with missense mutations in SLC2A1.