title: Severe phenotypic spectrum of biallelic mutations in PRRT2 gene.
abstract: BACKGROUND
  Heterozygous dominant mutations of PRRT2 have been associated with various types of paroxysmal neurological manifestations, including benign familial infantile convulsions and paroxysmal kinesigenic dyskinesia. The phenotype associated with biallelic mutations is not well understood as few cases have been reported.
  
  
  METHODS
  PRRT2 screening was performed by Sanger sequencing and quantitative multiplex PCR of short fluorescent fragments. A CGH array was used to characterise the size of the deletion at the 16p11.2 locus.
  
  
  RESULTS
  Five patients with homozygous or compound heterozygous deleterious PRRT2 gene mutations are described. These patients differ from those with a single mutation by their overall increased severity: (1) the combination of at least three different forms of paroxysmal neurological disorders within the same patient and persistence of paroxysmal attacks; (2) the occurrence of uncommon prolonged episodes of ataxia; and (3) the association of permanent neurological disorders including learning difficulties in four patients and cerebellar atrophy in 2.
  
  
  CONCLUSIONS
  Our observations expand the phenotype related to PRRT2 insufficiency, and highlight the complexity of the phenotype associated with biallelic mutations, which represents a severe neurological disease with various paroxysmal disorders and frequent developmental disabilities.
authors.affiliation: Service de Neuropédiatrie, CHU Gui de Chauliac, Montpellier, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Delcourt
authors.affiliation: Laboratoire de Génétique, AP-HP, Groupe Hospitalier Lariboisière-Fernand Widal, Paris, France INSERM UMR-S740; Université Paris 7 Denis Diderot, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Riant
authors.affiliation: Service de Neurologie Pédiatrique, CHU Timone Enfants, Marseille, France.
authors.forename: Josette
authors.initials: J
authors.lastname: Mancini
authors.affiliation: Service de Neurologie Pédiatrique, CHU Timone Enfants, Marseille, France Aix Marseille Université, INSERM, GMGF UMR_S 910, Marseille, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Milh
authors.affiliation: AP-HP, Unité d'épilepsie, Institut du Cerveau et de la Moelle épinière, Hôpital Pitié-Salpêtrière, Paris, France INSERM, UMRS 975, et CNRS 7225-Institut du Cerveau et de la Moelle épinière, Hôpital Pitié-Salpêtrière,Université Pierre et Marie Curie-Paris-6, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Navarro
authors.affiliation: Département des Maladies du Système Nerveux, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France CRICM, INSERM U1127, CNRS UMR 7225, UPMC UMR-S975, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Roze
authors.affiliation: Service de Médecine Psychologique Enfants et Adolescents, CHU Saint Eloi, Montpellier, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Humbertclaude
authors.affiliation: Neuropédiatrie HUG, Genève, Suisse.
authors.forename: Christian
authors.initials: C
authors.lastname: Korff
authors.affiliation: Neuropédiatrie, HFME, Hospices Civils de Lyon, Bron, France Université Lyon 1, F-69008 Lyon, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Des Portes
authors.affiliation: INSERM U901, Marseille, France Institut de Neurobiologie de la Méditerranée (INMED), Marseille, France UMR_S901, Université d'Aix-Marseille, Marseille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Szepetowski
authors.affiliation: Service de Neurologie Pédiatrique, AP-HP, Hôpital Trousseau, Paris, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Doummar
authors.affiliation: Service de Neuropédiatrie, CHU Gui de Chauliac, Montpellier, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Echenne
authors.affiliation: Team Genome and Cancer, Hematology Laboratory Assistance Publique-Hopitaux de Paris, Saint-Louis Hospital, Paris, France Inserm U944, Saint-Louis Hospital, Paris, France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Quintin
authors.affiliation: Service de Neuroradiologie, CHU Gui de Chauliac, Montpellier, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Leboucq
authors.affiliation: EA 4666, CHU d'Amiens-UPJV, Laboratoire de Génétique, Hôpital Sud, Amiens, France.
authors.forename: Rabbind
authors.initials: R
authors.lastname: Singh Amrathlal
authors.affiliation: EA 4666, CHU d'Amiens-UPJV, Laboratoire de Génétique, Hôpital Sud, Amiens, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Rochette
authors.affiliation: Service de Neuropédiatrie, CHU Gui de Chauliac, Montpellier, France INSERM U 1051, Institut des Neurosciences de Montpellier, Montpellier, France.
authors.forename: Agathe
authors.initials: A
authors.lastname: Roubertie
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000483:Alleles; D001259:Ataxia / Q000235:genetics; D001284:Atrophy / Q000235:genetics; D001927:Brain Diseases / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002819:Chorea / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005796:Genes / Q000235:genetics; D006801:Humans; D007223:Infant; D007859:Learning Disabilities / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C569370:PRRT2 protein, human
keywords: EPILEPSY; MENTAL RETARDATION; MOVEMENT DISORDERS; PAROXYSMAL DISORDER