title: Variable clinical expression in patients with mosaicism for KCNQ2 mutations.
abstract: Mutations in the KCNQ2 gene, encoding a potassium channel subunit, were reported in patients presenting epileptic phenotypes of varying severity. Patients affected by benign familial neonatal epilepsy (BFNE) are at the milder end of the spectrum, they are affected by early onset epilepsy but their subsequent neurological development is usually normal. Mutations causing BFNE are often inherited from affected parents. Early infantile epileptic encephalopathy type 7 (EIEE7) is at the other end of the severity spectrum and, although EIEE7 patients have early onset epilepsy too, their neurological development is impaired and they will present motor and intellectual deficiency. EIEE7 mutations occur de novo. Electrophysiological experiments suggested a correlation between the type of mutation and the severity of the disease but intra and interfamilial heterogeneity exist. Here, we describe the identification of KCNQ2 mutation carriers who had children affected with a severe epileptic phenotype, and found that these individuals were mosaic for the KCNQ2 mutation. These findings have important consequences for genetic counseling and indicate that neurological development can be normal in the presence of somatic mosaicism for a KCNQ2 mutation.
authors.affiliation: Inserm, UMR_S 910, Génétique Médicale et Génomique Fonctionnelle, Marseille, France.|Aix Marseille Université, GMGF, Faculté de Médecine, Marseille, France.|APHM, Hôpital d'Enfants de La Timone, Service de Neurologie Pédiatrique, Marseille, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Milh
authors.affiliation: Inserm, UMR_S 910, Génétique Médicale et Génomique Fonctionnelle, Marseille, France.|Aix Marseille Université, GMGF, Faculté de Médecine, Marseille, France.|APHM, Hôpital d'Enfants de La Timone, Département de Génétique Médicale, Marseille, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lacoste
authors.affiliation: Inserm, UMR_S 910, Génétique Médicale et Génomique Fonctionnelle, Marseille, France.|Aix Marseille Université, GMGF, Faculté de Médecine, Marseille, France.|APHM, Hôpital d'Enfants de La Timone, Département de Génétique Médicale, Marseille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Cacciagli
authors.affiliation: Inserm, UMR_S 910, Génétique Médicale et Génomique Fonctionnelle, Marseille, France.|Aix Marseille Université, GMGF, Faculté de Médecine, Marseille, France.
authors.forename: Affef
authors.initials: A
authors.lastname: Abidi
authors.affiliation: Inserm, UMR_S 910, Génétique Médicale et Génomique Fonctionnelle, Marseille, France.|Aix Marseille Université, GMGF, Faculté de Médecine, Marseille, France.|APHM, Hôpital d'Enfants de La Timone, Service de Neurologie Pédiatrique, Marseille, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Sutera-Sardo
authors.affiliation: Inserm, UMR_S 910, Génétique Médicale et Génomique Fonctionnelle, Marseille, France.|Aix Marseille Université, GMGF, Faculté de Médecine, Marseille, France.
authors.forename: Ilias
authors.initials: I
authors.lastname: Tzelepis
authors.affiliation: Département de Biochimie et Génétique, CHU d'Angers, Angers, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Colin
authors.affiliation: Inserm, UMR_S 910, Génétique Médicale et Génomique Fonctionnelle, Marseille, France.|Aix Marseille Université, GMGF, Faculté de Médecine, Marseille, France.|APHM, Hôpital d'Enfants de La Timone, Département de Génétique Médicale, Marseille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Badens
authors.affiliation: APHP, Hôpital Trousseau, Service de génétique clinique et Service de neuropédiatrie, Paris, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Afenjar
authors.affiliation: Clinique de Génétique, Hôpital Jeanne de Flandre, Lille, France.
authors.forename: Anne Dieux
authors.initials: AD
authors.lastname: Coeslier
authors.affiliation: Centre Hospitalier des Pays de Morlaix, Pédiatrie et Néonatalogie, Morlaix, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dailland
authors.affiliation: Département de Génétique Médicale, Hospices Civils de Lyon, Université Lyon 1, Lyon, France.
authors.forename: Gaetan
authors.initials: G
authors.lastname: Lesca
authors.affiliation: Inserm, UMR_S 910, Génétique Médicale et Génomique Fonctionnelle, Marseille, France.|Aix Marseille Université, GMGF, Faculté de Médecine, Marseille, France.|APHM, Hôpital d'Enfants de La Timone, Département de Génétique Médicale, Marseille, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Philip
authors.affiliation: Inserm, UMR_S 910, Génétique Médicale et Génomique Fonctionnelle, Marseille, France.|Aix Marseille Université, GMGF, Faculté de Médecine, Marseille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Villard
mesh_terms: D058540:Aicardi Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D020936:Epilepsy, Benign Neonatal / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005091:Exons; D005260:Female; D015870:Gene Expression; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D040582:Inheritance Patterns; D051658:KCNQ2 Potassium Channel / Q000235:genetics*; D008297:Male; D009030:Mosaicism; D009154:Mutation; D010641:Phenotype; D012720:Severity of Illness Index; D013036:Spasms, Infantile / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology
chemical_list: D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human
keywords: BFNE; EIEE7; KCNQ2; encephalopathy; epilepsy; genetic counseling; somatic mosaicism