title: PRRT2 mutations: a major cause of paroxysmal kinesigenic dyskinesia in the European population.
abstract: OBJECTIVE
  Paroxysmal kinesigenic dyskinesia (PKD) is a rare disorder characterized by recurrent attacks of hyperkinetic movements. PKD can be isolated or associated with benign infantile seizures as part of the infantile convulsions with choreoathetosis (ICCA) syndrome. Mutations in the PRRT2 gene were recently identified in patients with PKD and ICCA. We studied the prevalence of PRRT2 mutations and characteristics of the patients in a European population of patients with PKD and ICCA.
  
  
  METHODS
  Patients were recruited through the 1996-2011 database of our DNA bank, to which physicians refer DNA with a putative diagnosis and clinical information. Two movement disorders experts reviewed the information on patients with a putative diagnosis of PKD. Patients who fulfilled the criteria for PKD and ICCA were included. The PRRT2 coding sequence was analyzed by direct sequencing.
  
  
  RESULTS
  Among 42 index cases of unrelated families referred with a putative diagnosis of PKD, a total of 34 patients, including 32 with isolated PKD and 2 with ICCA, were selected for genetic analysis. Mutations introducing premature termination codons were identified in 22 of 34 patients including 13 of 14 families and 9 of 20 patients with sporadic cases. The previously described c.649dupC/pArg217ProfsX8 and c.629dupC/pAla211SerfsX14 were present, respectively, in 17 patients and 1 patient; we also report 3 novel mutations: c.649delC/pArg217GlufsX12 in 2 patients, and c.562C>T/pGln188X and c.649C>T/pArg217X, each in 1 patient. The group with mutations was characterized by a younger age at onset (9 years) compared with the patients without mutations (15 years; p < 0.01).
  
  
  CONCLUSIONS
  Mutations in PRRT2 are a major cause of PKD in familial and sporadic cases in the European population.
authors: INSERM, UMRS 975, Hôpital Pitié-Salpêtrière, Paris, France.
authors: Aurélie
authors: A
authors: Méneret
authors: David
authors: D
authors: Grabli
authors: Christel
authors: C
authors: Depienne
authors: Cécile
authors: C
authors: Gaudebout
authors: Fabienne
authors: F
authors: Picard
authors: Alexandra
authors: A
authors: Dürr
authors: Isabelle
authors: I
authors: Lagroua
authors: Delphine
authors: D
authors: Bouteiller
authors: Cyril
authors: C
authors: Mignot
authors: Diane
authors: D
authors: Doummar
authors: Mathieu
authors: M
authors: Anheim
authors: Christine
authors: C
authors: Tranchant
authors: Pierre
authors: P
authors: Burbaud
authors: Charles Pierre
authors: CP
authors: Jedynak
authors: Domitille
authors: D
authors: Gras
authors: Dominique
authors: D
authors: Steschenko
authors: David
authors: D
authors: Devos
authors: Thierry
authors: T
authors: Billette de Villemeur
authors: Marie
authors: M
authors: Vidailhet
authors: Alexis
authors: A
authors: Brice
authors: Emmanuel
authors: E
authors: Roze
mesh_terms: D000328:Adult; D017668:Age of Onset; D002819:Chorea / Q000175:diagnosis / Q000235:genetics*; D020820:Dyskinesias / Q000175:diagnosis / Q000235:genetics*; D020936:Epilepsy, Benign Neonatal / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D012640:Seizures / Q000175:diagnosis / Q000235:genetics*; D013577:Syndrome; D044465:White People / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C569370:PRRT2 protein, human