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Short Report
Severe phenotypic spectrum of biallelic mutations in PRRT2 gene
  1. Marion Delcourt1,
  2. Florence Riant2,3,
  3. Josette Mancini4,
  4. Mathieu Milh4,5,
  5. Vincent Navarro6,7,
  6. Emmanuel Roze8,9,
  7. Véronique Humbertclaude10,
  8. Christian Korff11,
  9. Vincent Des Portes12,13,
  10. Pierre Szepetowski14,15,16,
  11. Diane Doummar17,
  12. Bernard Echenne1,
  13. Samuel Quintin18,19,
  14. Nicolas Leboucq20,
  15. Rabbind Singh Amrathlal21,
  16. Jacques Rochette21,
  17. Agathe Roubertie1,22
  1. 1Service de Neuropédiatrie, CHU Gui de Chauliac, Montpellier, France
  2. 2Laboratoire de Génétique, AP-HP, Groupe Hospitalier Lariboisière-Fernand Widal, Paris, France
  3. 3INSERM UMR-S740; Université Paris 7 Denis Diderot, Paris, France
  4. 4Service de Neurologie Pédiatrique, CHU Timone Enfants, Marseille, France
  5. 5Aix Marseille Université, INSERM, GMGF UMR_S 910, Marseille, France
  6. 6AP-HP, Unité d’épilepsie, Institut du Cerveau et de la Moelle épinière, Hôpital Pitié-Salpêtrière, Paris, France
  7. 7INSERM, 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
  8. 8Département des Maladies du Système Nerveux, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France
  9. 9CRICM, INSERM U1127, CNRS UMR 7225, UPMC UMR-S975, Paris, France
  10. 10Service de Médecine Psychologique Enfants et Adolescents, CHU Saint Eloi, Montpellier, France
  11. 11Neuropédiatrie HUG, Genève, Suisse
  12. 12Neuropédiatrie, HFME, Hospices Civils de Lyon, Bron, France
  13. 13Université Lyon 1, F-69008 Lyon, France
  14. 14INSERM U901, Marseille, France
  15. 15Institut de Neurobiologie de la Méditerranée (INMED), Marseille, France
  16. 16UMR_S901, Université d'Aix-Marseille, Marseille, France
  17. 17Service de Neurologie Pédiatrique, AP-HP, Hôpital Trousseau, Paris, France
  18. 18Team Genome and Cancer, Hematology Laboratory Assistance Publique-Hopitaux de Paris, Saint-Louis Hospital, Paris, France
  19. 19Inserm U944, Saint-Louis Hospital, Paris, France
  20. 20Service de Neuroradiologie, CHU Gui de Chauliac, Montpellier, France
  21. 21EA 4666, CHU d'Amiens—UPJV, Laboratoire de Génétique, Hôpital Sud, Amiens, France
  22. 22INSERM U 1051, Institut des Neurosciences de Montpellier, Montpellier, France
  1. Correspondence to Dr Agathe Roubertie, Service de Neuropédiatrie, CHU Gui de Chauliac, 80 Avenue Fliche, Montpellier 34295, France; A-roubertie{at}


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.


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