title: PCDH19-related epilepsy in two mosaic male patients.
abstract: PCDH19 gene mutations have been recently associated with an epileptic syndrome characterized by focal and generalized seizures. The PCDH19 gene (Xq22.1) has an unusual X-linked inheritance with a selective involvement for female subjects. A cellular interference mechanism has been hypothesized and male patients can manifest epilepsy only in the case of a mosaicism. So far about 100 female patients, and only one symptomatic male have been described. Using targeted next generation sequencing (NGS) approach we found a PCDH19 point mutation in two male patients with a clinical picture suggestive of PCDH19-related epilepsy. The system allowed us to verify that the two c.1352 C>T; p.(Pro451Leu) and c.918C>G; p.(Tyr306*) variants occurred in mosaic status. Mutations were confirmed by Sanger sequencing and quantified by real-time polymerase chain reaction (PCR). Up to now, the traditional molecular screening for PCDH19-related epilepsy has been targeted to all females with early onset epilepsy with or without cognitive impairment. Male patients were generally excluded. We describe for the first time two mosaic PCDH19 point mutations in two male patients with a clinical picture suggestive of PCDH19-related epilepsy. This finding opens new opportunities for the molecular diagnoses in patients with a peculiar type of epilepsy that remains undiagnosed in male patients.
authors.affiliation: Department of Neurosciences, Unit of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Terracciano
authors.affiliation: Department of Neurosciences, Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Trivisano
authors.affiliation: Department of Neurosciences, Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Cusmai
authors.affiliation: Department of Neurosciences, Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: De Palma
authors.affiliation: Department of Neurosciences, Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Fusco
authors.affiliation: Department of Neurosciences, Unit of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Compagnucci
authors.affiliation: Department of Neurosciences, Unit of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.affiliation: Department of Neurosciences, Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Vigevano
authors.affiliation: Department of Neurosciences, Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Specchio
mesh_terms: D015820:Cadherins / Q000235:genetics*; D002675:Child, Preschool; D004827:Epilepsy / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D017354:Point Mutation / Q000235:genetics*; D000091363:Protocadherins
chemical_list: D015820:Cadherins; C438605:PCDH19 protein, human; D000091363:Protocadherins
keywords: Epilepsy; Male; NGS; Next generation sequencing; PCDH19