Suls A , Dedeken P , Goffin K , Van Esch H , Dupont P , Cassiman D , Kempfle J , Wuttke TV , Weber Y , Lerche H , Afawi Z , Vandenberghe W , Korczyn AD , Berkovic SF , Ekstein D , Kivity S , Ryvlin P , Claes LR , Deprez L , Maljevic S , Vargas A , Van Dyck T , Goossens D , Del-Favero J , Van Laere K , De Jonghe P , Van Paesschen W .

	Fig. 1. Pedigree of families A–D. + = normal allele; m = mutated allele. Individuals carrying a heterozygous mutation in SLC2A1 are indicated with +/m. Individuals indicated with +/+ do not carry a mutated allele. Individuals without indication were not available for screening.
	Fig. 2. The GLUT1 protein structure consisting of 12 transmembrane domains and intracellular amino- and carboxy-termini (Mueckler et al., 1985). GLUT1 DS (Klepper and Leiendecker, 2007) and PED/epilepsy mutations are marked on this figure (yellow colored circles). The PED/epilepsy mutations are boxed. The solid bars indicate the locations of the intron–exon boundaries in the GLUT1 gene. Splice site mutations are indicated at these solid bars with asterisk.
	Fig. 3. The interictal EEG of patient A. III.24 showed high voltage anterior predominant generalized spike-wave complexes on a normal background. Time base: 30 mm/s, sensitivity: see calibration: 200 µV/cm, high cut: 30.0 Hz, low cut: 0.5 Hz.
	Fig. 4. During hyperventilation, patient A.V.1 had a brief absence with high voltage 3 Hz generalized spike wave discharges during 6 s on EEG. Time base: 30 mm/s, sensitivity (of original recording): 300 µV/cm, high cut: 35.0 Hz, low cut: 0.5 Hz.
	Fig. 5. Functional studies to investigate a change in glucose uptake, protein stability or trafficking by the three point mutations in Xenopus oocytes. (A) Plotted is the glucose uptake versus 3-O-methyl-D-glucose (OMG) concentration. The uptake was significantly reduced for all three mutations (shown are representative results recorded from one batch of 3 × 10 oocytes for each glucose concentration, means ± SEM, *P < 0.05, ***P < 0.001). (B) Kinetic analysis of glucose uptakes in oocytes according to Lineweaver-Burk. The linear function 1/V (1/[S]) = 1/Vmax + Km/Vmax*1/[S] was fit to the data points, with [S] being the concentration of OMG, V the uptake velocity in pmol/oocyte/min obtained for a given [S], Vmax the maximal uptake velocity reflecting the maximal transport capacity of GLUT1 and Km the Michaelis-Menten constant representing the concentration [S] for which the half-maximal uptake velocity (V1/2) is reached. Vmax and Km were calculated from the y- and x-interceptions of the linear fits, with the y-intercept equalling 1/Vmax and the x-intercept −1/Km. The following values were obtained (Vmax is given in pmol/oocyte/min and Km in mM): WT: Vmax = 319 ± 16, Km = 19 ± 1; S95I: Vmax = 86 ± 2, Km = 11 ± 1; V140M: Vmax = 26 ± 11, Km = 15 ± 9; N317T: Vmax = 60 ± 18, Km = 15 ± 7. (C) Western blots obtained from oocytes injected with equal amounts of cRNA showed a similar amount of protein for all mutations and the WT, but no respective band for oocytes injected with H2O as a negative control; α-tubulin was used as a loading control. (D) Immunocytochemical analysis of injected oocytes using an anti-GLUT1 antibody revealed similar stainings of the surface membranes for all four clones.
	Fig. 6. SPM T-map of the analysis of patients versus controls. Relative hypermetabolism in the patient group compared with controls is indicated in yellow/red, hypometabolism in blue/green. Results are projected on an average spatially normalized in-house T1 image of healthy controls. R = right; L = left.
	Fig. 7. Subtraction ictal SPECT coregistered to MRI (SISCOM) (1, 3) during an episode of PED and interictal FDG PET (2, 4) in patient A.III.24. Top row: coronal images, bottom row: axial images. The episode of PED lasted in total around 17 min, and was interrupted by brief moments of no abnormal movements. The dyskinesia mainly involved the legs, left more than right and pelvis (see video; A.III.24 Ictal SPECT during PED, in supplementary data). The injection was given around three minutes after onset. The SISCOM (threshold: + 2 SD) showed an area of hyperperfusion in the left putamen (blue cross in 1), which coincided with interictal putaminal hypermetabolism (blue cross in 2). The largest and most hyperintense hyperperfusion cluster was in the right primary motor area of the leg (blue cross in 3), which coincided with an area of hypometabolism in the interictal FDG PET (blue cross in 4). All images are coregistered. Hyperperfusion clusters are projected on the patient's MPRAGE images. R = right; L = left.

Alderborn, Determination of single-nucleotide polymorphisms by real-time pyrophosphate DNA sequencing. 2000, Pubmed

Alderborn, Determination of single-nucleotide polymorphisms by real-time pyrophosphate DNA sequencing. 2000, Pubmed
Auburger, A gene for autosomal dominant paroxysmal choreoathetosis/spasticity (CSE) maps to the vicinity of a potassium channel gene cluster on chromosome 1p, probably within 2 cM between D1S443 and D1S197. 1996, Pubmed
Berkovic, Paroxysmal movement disorders and epilepsy: links across the channel. 2000, Pubmed
Bhatia, Paroxysmal exercise-induced dystonia: eight new sporadic cases and a review of the literature. 1997, Pubmed
Bing, [A family with exercise-induced paroxysmal dystonia and childhood absence epilepsy]. 2005, Pubmed
Brockmann, X-linked paroxysmal dyskinesia and severe global retardation caused by defective MCT8 gene. 2005, Pubmed
Brockmann, Autosomal dominant glut-1 deficiency syndrome and familial epilepsy. 2001, Pubmed , Xenbase
Cottingham, Faster sequential genetic linkage computations. 1993, Pubmed
De Vivo, Defective glucose transport across the blood-brain barrier as a cause of persistent hypoglycorrhachia, seizures, and developmental delay. 1991, Pubmed
Demirkiran, Paroxysmal dyskinesias: clinical features and classification. 1995, Pubmed
Deprez, Familial occipitotemporal lobe epilepsy and migraine with visual aura: linkage to chromosome 9q. 2007, Pubmed
Du, Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder. 2005, Pubmed , Xenbase
Dupont, Ictal perfusion patterns associated with single MRI-visible focal dysplastic lesions: implications for the noninvasive delineation of the epileptogenic zone. 2006, Pubmed
Friedman, Atypical GLUT1 deficiency with prominent movement disorder responsive to ketogenic diet. 2006, Pubmed
Guerrini, Autosomal recessive rolandic epilepsy with paroxysmal exercise-induced dystonia and writer's cramp: delineation of the syndrome and gene mapping to chromosome 16p12-11.2. 1999, Pubmed
Guerrini, Early-onset absence epilepsy and paroxysmal dyskinesia. 2002, Pubmed
Iserovich, Changes in glucose transport and water permeability resulting from the T310I pathogenic mutation in Glut1 are consistent with two transport channels per monomer. 2002, Pubmed , Xenbase
Kamm, New family with paroxysmal exercise-induced dystonia and epilepsy. 2007, Pubmed
Kato, Paroxysmal kinesigenic choreoathetosis: from first discovery in 1892 to genetic linkage with benign familial infantile convulsions. 2006, Pubmed
Kikuchi, Paroxysmal kinesigenic choreoathetosis (PKC): confirmation of linkage to 16p11-q21, but unsuccessful detection of mutations among 157 genes at the PKC-critical region in seven PKC families. 2007, Pubmed
Klepper, Bench meets bedside: a 10-year-old girl and amino acid residue glycine 75 of the facilitative glucose transporter GLUT1. 2005, Pubmed
Klepper, GLUT1 deficiency syndrome--2007 update. 2007, Pubmed
Klepper, Autosomal dominant transmission of GLUT1 deficiency. 2001, Pubmed
Klepper, Functional consequences of the autosomal dominant G272A mutation in the human GLUT1 gene. 2001, Pubmed , Xenbase
Klepper, Effects of the ketogenic diet in the glucose transporter 1 deficiency syndrome. 2004, Pubmed
Kluge, Changes in perfusion pattern using ECD-SPECT indicate frontal lobe and cerebellar involvement in exercise-induced paroxysmal dystonia. 1998, Pubmed
Lance, Familial paroxysmal dystonic choreoathetosis of Mount and Reback and its differentiation from related syndromes. 1977, Pubmed
Leary, Seizure characterization and electroencephalographic features in Glut-1 deficiency syndrome. 2003, Pubmed
Lee, Association of infantile convulsions with paroxysmal dyskinesias (ICCA syndrome): confirmation of linkage to human chromosome 16p12-q12 in a Chinese family. 1998, Pubmed
Margari, Familial paroxysmal exercise-induced dyskinesia and benign epilepsy: a clinical and neurophysiological study of an uncommon disorder. 2000, Pubmed
Mueckler, Sequence and structure of a human glucose transporter. 1985, Pubmed
Münchau, A new family with paroxysmal exercise induced dystonia and migraine: a clinical and genetic study. 2000, Pubmed
Nagamitsu, Multicenter study of paroxysmal dyskinesias in Japan--clinical and pedigree analysis. 1999, Pubmed
Nardocci, Typical and atypical forms of paroxysmal choreoathetosis. 1989, Pubmed
Neville, Exercise induced steroid dependent dystonia, ataxia, and alternating hemiplegia associated with epilepsy. 1998, Pubmed
Overweg-Plandsoen, GLUT-1 deficiency without epilepsy--an exceptional case. 2003, Pubmed
Pascual, Imaging the metabolic footprint of Glut1 deficiency on the brain. 2002, Pubmed
Plant, Familial paroxysmal dystonia induced by exercise. 1984, Pubmed
Rainier, Myofibrillogenesis regulator 1 gene mutations cause paroxysmal dystonic choreoathetosis. 2004, Pubmed
Signorini, Rapid assessment of regional cerebral metabolic abnormalities in single subjects with quantitative and nonquantitative [18F]FDG PET: A clinical validation of statistical parametric mapping. 1999, Pubmed
Swoboda, Paroxysmal kinesigenic dyskinesia and infantile convulsions: clinical and linkage studies. 2000, Pubmed
Szepetowski, Familial infantile convulsions and paroxysmal choreoathetosis: a new neurological syndrome linked to the pericentromeric region of human chromosome 16. 1997, Pubmed
Van Laere, Metabolic imaging of anterior capsular stimulation in refractory obsessive-compulsive disorder: a key role for the subgenual anterior cingulate and ventral striatum. 2006, Pubmed
Wali, Paroxysmal hemidystonia induced by prolonged exercise and cold. 1992, Pubmed
Wang, Glut-1 deficiency syndrome: clinical, genetic, and therapeutic aspects. 2005, Pubmed
Wang, Functional studies of threonine 310 mutations in Glut1: T310I is pathogenic, causing Glut1 deficiency. 2003, Pubmed , Xenbase
Weber, GLUT1 mutations are a cause of paroxysmal exertion-induced dyskinesias and induce hemolytic anemia by a cation leak. 2008, Pubmed , Xenbase
Weckx, novoSNP, a novel computational tool for sequence variation discovery. 2005, Pubmed
Wong, Disease-associated Glut1 single amino acid substitute mutations S66F, R126C, and T295M constitute Glut1-deficiency states in vitro. 2007, Pubmed