1. Mutations and Deletions in PCDH19 Account for Various Familial or Isolated Epilepsies in Females
- Author
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Eric LeGuern, François Rivier, Brigitte Gilbert-Dussardier, Denys Chaigne, Delphine Bouteiller, Karine Poirier, Agathe Roubertie, Anne Dusser, Sandra Whalen, Marie Bru, Dominique Steschenko, Oriane Trouillard, Isabelle Gourfinkel-An, Stéphanie Baulac, Alexis Arzimanoglou, Agnès Gautier, Dorota Hoffman-Zacharska, Christel Depienne, Anna Kaminska, Hélène Maurey, Cyril Mignot, Gaetan Lesca, Annie Lannuzel, Marilyn Lackmy-Port-Lis, Rima Nabbout, Patrick Berquin, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Pôle d'Epileptologie, AP-HP, Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Service de Neuropédiatrie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de neuropédiatrie, CHU Hôpital Nord Amiens, Département de Neuropédiatrie, CHU Necker - Enfants Malades [AP-HP], Clinique Sainte-Odile, Strasbourg, Unité de Neurologie Pédiatrique, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Serice de Neuropédiatrie, Institute of Mother and Child Department of Medical Genetics, Department of neurology, CHU Pointe-à-Pitre/Abymes [Guadeloupe], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de neurologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Hôpital Mère-Enfant, CHU de Nantes, Service de Genetique medicale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Hôpital, CHU Trousseau [APHP], Pavillon E, Laboratoire de Genetique, Unité d'Epileptologie Pédiatrique, Service de Neurologie Pédiatrique et des Maladies Métaboliques, AP-HP, Hôpital Robert Debré, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Amiens-Picardie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière ( CRICM ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, and Centre hospitalier universitaire de Poitiers ( CHU Poitiers )
- Subjects
Adult ,Male ,PCDH19 ,Adolescent ,Febrile seizures ,Protocadherin ,Mutation in Brief ,Biology ,medicine.disease_cause ,03 medical and health sciences ,Exon ,Epilepsy ,Young Adult ,0302 clinical medicine ,Genetics ,medicine ,Humans ,Family history ,Child ,Genetics (clinical) ,X chromosome ,cognitive function ,030304 developmental biology ,0303 health sciences ,Mutation ,Polymorphism, Genetic ,Point mutation ,Life Sciences ,Infant ,Exons ,Middle Aged ,medicine.disease ,Cadherins ,Protocadherins ,Pedigree ,Child, Preschool ,Female ,microdeletion ,Generalized epilepsy with febrile seizures plus ,030217 neurology & neurosurgery ,Gene Deletion - Abstract
International audience; Mutations in PCDH19, encoding protocadherin 19 on chromosome X, cause familial epilepsy and mental retardation limited to females or Dravet-like syndrome. Heterozygous females are affected while hemizygous males are spared, this unusual mode of inheritance being probably due to a mechanism called cellular interference. To extend the mutational and clinical spectra associated with PCDH19, we screened 150 unrelated patients (113 females) with febrile and afebrile seizures for mutations or rearrangements in the gene. Fifteen novel point mutations were identified in 15 female patients (6 sporadic and 9 familial cases). In addition, qPCR revealed two whole gene deletions and one partial deletion in 3 sporadic female patients. Clinical features were highly variable but included almost constantly a high sensitivity to fever and clusters of brief seizures. Interestingly, cognitive functions were normal in several family members of 2 families: the familial condition in family 1 was suggestive of Generalized Epilepsy with Febrile Seizures Plus (GEFS+) whereas all three affected females had partial cryptogenic epilepsy. These results show that mutations in PCDH19 are a relatively frequent cause of epilepsy in females and should be considered even in absence of family history and/or mental retardation.
- Published
- 2011