title: Severe episodic neurological deficits and permanent mental retardation in a child with a novel FHM2 ATP1A2 mutation.
abstract: OBJECTIVE
  Attacks of familial hemiplegic migraine (FHM) are usually associated with transient, completely reversible symptoms. Here, we studied the ATP1A2 FHM2 gene in a young girl with episodes of both very severe and transient neurological symptoms that were triggered by mild head trauma as well as permanent mental retardation. Her family members suffered from hemiplegic and confusional migraine attacks.
  
  
  METHODS
  Mutation analysis of the ATP1A2 gene was performed by direct sequencing of all exons and flanking intronic regions, using genomic DNA of the proband. Functional consequences of the mutation were analyzed by cellular survival assays.
  
  
  RESULTS
  We identified a novel G615R ATP1A2 mutation in the proband and several of her family members. Functional analysis of mutant Na,K-ATPase in cellular survival assays showed a complete loss-of-function effect.
  
  
  CONCLUSIONS
  Permanent mental retardation in children may be caused by ATP1A2 mutations.
authors.affiliation: Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: K R J
authors.initials: KR
authors.lastname: Vanmolkot
authors.forename: H
authors.initials: H
authors.lastname: Stroink
authors.forename: J B
authors.initials: JB
authors.lastname: Koenderink
authors.forename: E E
authors.initials: EE
authors.lastname: Kors
authors.forename: J J M W
authors.initials: JJ
authors.lastname: van den Heuvel
authors.forename: E H
authors.initials: EH
authors.lastname: van den Boogerd
authors.forename: A H
authors.initials: AH
authors.lastname: Stam
authors.forename: J
authors.initials: J
authors.lastname: Haan
authors.forename: B B A
authors.initials: BB
authors.lastname: De Vries
authors.forename: G M
authors.initials: GM
authors.lastname: Terwindt
authors.forename: R R
authors.initials: RR
authors.lastname: Frants
authors.forename: M D
authors.initials: MD
authors.lastname: Ferrari
authors.forename: A M J M
authors.initials: AM
authors.lastname: van den Maagdenberg
mesh_terms: D001120:Arginine / Q000235:genetics; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002648:Child; D004252:DNA Mutational Analysis / Q000379:methods; D004569:Electroencephalography / Q000379:methods; D005260:Female; D015870:Gene Expression / Q000502:physiology; D005998:Glycine / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D020325:Migraine with Aura / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D016296:Mutagenesis / Q000502:physiology; D009154:Mutation; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*; D014162:Transfection / Q000379:methods
chemical_list: D001120:Arginine; C498531:ATP1A2 protein, human; D000254:Sodium-Potassium-Exchanging ATPase; D005998:Glycine