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West syndrome, microcephaly, grey matter heterotopia and hypoplasia of corpus callosum due to a novel ARFGEF2 mutation
  1. Ehud Banne1,
  2. Osama Atawneh2,
  3. Marco Henneke3,
  4. Knut Brockmann3,
  5. Jutta Gärtner3,
  6. Orly Elpeleg1,
  7. Simon Edvardson1
  1. 1Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, Jerusalem, Israel
  2. 2Department of Pediatrics, Palestinian Red Cross Society Hospital, Hebron, Palestine
  3. 3Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center, Göttingen, Germany
  1. Correspondence to Professor Simon Edvardson, Department of Genetic and Metabolic Diseases, Hadassah, Hebrew University Medical Center, Jerusalem 91120, Israel; simon{at}hadassah.org.il

Abstract

West syndrome (WS) is an epileptic encephalopathy of childhood, defined by the presence of clustered spasms usually occurring before the age of 1 year, hypsarrhythmia on EEG that is notoriously difficult to define, and developmental arrest or regression. The incidence of WS is 1:3200 live births with an aetiology-dependent prognosis. Up to 80% of children with symptomatic WS suffer from mental retardation, and approximately 50% develop Lennox–Gastaut syndrome. Using homozygosity mapping followed by exome sequencing, we identified a ADP-ribosylation factor (ARF) guanine nucleotide-exchange factor two (brefeldin A-inhibited) (ARFGEF2) mutation in five related infants with WS. ARFGEF2 is involved in the activation of ARFs by accelerating replacement of bound guanosine diphosphate (GDP) with Guanosine triphosphate (GTP), and is involved in Golgi transport. A mutation in ARFGEF2 has been previously described only once, causing microcephaly and periventricular heterotopia. Here, we describe a novel ARFGEF2 mutation in five related patients presenting with WS, microcephaly, periventricular heterotopia and thin corpus callosum.

  • Genetics
  • Epilepsy and seizures
  • Neurosciences
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