title: Vanishing white matter disease in French-Canadian patients from Quebec.
abstract: BACKGROUND
  Vanishing white matter disease is an autosomal recessive leukodystrophy caused by mutations in any of the five genes encoding the subunits of the eukaryotic translation initiation factor 2B. Most of the reported patients are of North American and European ancestry.
  
  
  OBJECTIVE
  The objective of the study was to review the clinical, radiological, and molecular characteristics of vanishing white matter disease in a cohort of French-Canadian patients.
  
  
  METHODS
  Between 2004 and March 2012, five French-Canadian (non-Cree) patients from Quebec were clinically and genetically diagnosed with vanishing white matter disease within three Montreal Neurogenetics and Leukodystrophy clinics. Their clinical presentation and evolution, demographic characteristics, genetic mutations, and imaging were reviewed and compared with what is known in the literature.
  
  
  RESULTS
  Sequencing of the exons and intronic boundaries of the EIF2B1-5 genes revealed a rare 260C>T (A87V) missense mutation in EIF2B3 in two homozygous patients and one compound heterozygous patient. This mutation was previously reported in only one patient in the literature. The carrier frequency is unknown. Also, three of five Quebec patients had an extremely rare vanishing white matter disease presentation of migraines with transient neurological abnormalities.
  
  
  CONCLUSIONS
  The 260C>T (A87V) mutation in exon 3 of the EIF2B3 gene is likely a founder mutation for vanishing white matter disease in Quebec. Transient hemiparesthesia and hemiparesis episodes accompanied by headaches as presenting abnormalities of vanishing white matter disease are usually rare but seemed to be more frequent among the French-Canadian Quebec patients. They seemed to be preceded by periods of stress.
authors: Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada. Electronic address: marie.eve.robinson@gmail.com.
authors: Marie-Ève
authors: MÈ
authors: Robinson
authors: Department of Neurosciences, CHU-Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada; Department of Pediatrics, CHU-Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada.
authors: Elsa
authors: E
authors: Rossignol
authors: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University Health Center, Montreal, Quebec, Canada; Department of Human Genetics, Montreal Neurological Institute, McGill University Health Center, Montreal, Quebec, Canada.
authors: Bernard
authors: B
authors: Brais
authors: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University Health Center, Montreal, Quebec, Canada.
authors: Guy
authors: G
authors: Rouleau
authors: Centre Hospitalier de Trois-Rivières, Trois-Rivières, Quebec, Canada.
authors: Jean-François
authors: JF
authors: Arbour
authors: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University Health Center, Montreal, Quebec, Canada; Department of Pediatrics, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada; Department of Pediatric Neurology, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada.
authors: Geneviève
authors: G
authors: Bernard
mesh_terms: D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D020717:Eukaryotic Initiation Factor-2B / Q000235:genetics*; D005260:Female; D005602:France / Q000208:ethnology; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000208:ethnology / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D008297:Male; D011792:Quebec / Q000208:ethnology
chemical_list: D020717:Eukaryotic Initiation Factor-2B
keywords: EIF2B3; Quebec; founder mutation; headaches; vanishing white matter disease