title: Uncovering microdeletions in patients with severe Glut-1 deficiency syndrome using SNP oligonucleotide microarray analysis.
abstract: 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 45Kb to 4.51Mb, and all were identified using high resolution single nucleotide polymorphism (SNP) oligonucleotide microarray analysis (SOMA). Cases with microdeletions 82Kb 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.
authors.affiliation: Department of Pathology and Cell Biology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA. BL2185@Columbia.edu
authors.forename: Brynn
authors.initials: B
authors.lastname: Levy
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Paivi M
authors.initials: PM
authors.lastname: Ullner
authors.forename: Kristin
authors.initials: K
authors.lastname: Engelstad
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Odelia
authors.initials: O
authors.lastname: Nahum
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
authors.forename: Darryl C
authors.initials: DC
authors.lastname: De Vivo
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000235:genetics; D004200:Diseases in Twins / Q000235:genetics; D004827:Epilepsy / Q000235:genetics; D005260:Female; D051272:Glucose Transporter Type 1 / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008831:Microcephaly / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion; D013577:Syndrome; D055815:Young Adult
chemical_list: D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human