A novel SLC2A1 mutation linking hemiplegic migraine with alternating hemiplegia of childhood.
BACKGROUND
Hemiplegic migraine (HM) and alternating hemiplegia of childhood (AHC) are rare episodic neurological brain disorders with partial clinical and genetic overlap. Recently, ATP1A3 mutations were shown to account for the majority of AHC patients. In addition, a mutation in the SLC2A1 gene was reported in a patient with atypical AHC. We therefore investigated whether mutations in these genes may also be involved in HM. Furthermore, we studied the role of SLC2A1 mutations in a small set of AHC patients without ATP1A3 mutations.


METHODS
We screened 42 HM patients (21 familial and 21 sporadic patients) for ATP1A3 and SLC2A1 mutations. In addition, four typical AHC patients and one atypical patient with overlapping symptoms of both disorders were screened for SLC2A1 mutations.


RESULTS
A pathogenic de novo SLC2A1 mutation (p.Gly18Arg) was found in the atypical patient with overlapping symptoms of AHC and hemiplegic migraine. No mutations were found in the HM and the other AHC patients.


CONCLUSIONS
Screening for a mutation in the SLC2A1 gene should be considered in patients with a complex phenotype with overlapping symptoms of hemiplegic migraine and AHC.
Department of Human Genetics, Leiden University Medical Centre, the Netherlands.
Claudia M
CM
Weller
Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, the Netherlands.
Wilhelmina G
WG
Leen
Neurosciences Unit, Institute of Child Health, UCL Medical School and Great Ormond Street Hospital for Children NHS Trust, UK.
Brian G R
BG
Neville
UCL Institute of Neurology, UK.
John S
JS
Duncan
Department of Human Genetics, Leiden University Medical Centre, the Netherlands.
Boukje
B
de Vries
Department of Human Genetics, Leiden University Medical Centre, the Netherlands.
Marije A
MA
Geilenkirchen
Neurosciences Unit, Institute of Child Health, UCL Medical School and Great Ormond Street Hospital for Children NHS Trust, UK Department of Neurology, Rijnland Hospital, the Netherlands.
Joost
J
Haan
Department of Human Genetics, Institute for Genetic and Metabolic Disease, Radboud University Medical Centre, the Netherlands.
Erik-Jan
EJ
Kamsteeg
Department of Neurology, Leiden University Medical Center, the Netherlands.
Michel D
MD
Ferrari
Department of Human Genetics, Leiden University Medical Centre, the Netherlands Department of Neurology, Leiden University Medical Center, the Netherlands.
Arn M J M
AM
van den Maagdenberg
Department of Paediatric Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, the Netherlands.
Michèl A A P
MA
Willemsen
Department of Human Genetics, Institute for Genetic and Metabolic Disease, Radboud University Medical Centre, the Netherlands.
Hans
H
Scheffer
Department of Neurology, Leiden University Medical Center, the Netherlands G.M.Terwindt@lumc.nl.
Gisela M
GM
Terwindt
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D051272:Glucose Transporter Type 1 / Q000235:genetics*; D006429:Hemiplegia / Q000235:genetics*; D006801:Humans; D020325:Migraine with Aura / Q000235:genetics*; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D055815:Young Adult
D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human
  SLC2A1 gene; GLUT1 deficiency syndrome; Hemiplegic migraine (HM); alternating hemiplegia of childhood (AHC); exercise-induced dystonia