Lack of pathogenic mutations in six patients with MMPSI

Maria Rosaria De Filippo; Francesca Rizzo; Giovanna Marchese; Giorgio Giurato; Giovanni Nassa; Maria Ravo; Roberta Tarallo; Erica Pironti; Marilena Vecchi; Giovanni Crichiutti; Giorgio Capizzi; Alberto Verrotti; Alessandro Weisz; Giangennaro Coppola

doi:10.1016/j.eplepsyres.2013.11.007

Lack of pathogenic mutations in six patients with MMPSI

Epilepsy Res. 2014 Feb;108(2):340-4. doi: 10.1016/j.eplepsyres.2013.11.007. Epub 2013 Nov 16.

Affiliations

¹ Laboratory of Molecular Medicine and Genomics, Department of Medicine and Surgery, University of Salerno, Baronissi, Italy; Fondazione IRCCS SDN, 80143 Napoli, Italy.
² Laboratory of Molecular Medicine and Genomics, Department of Medicine and Surgery, University of Salerno, Baronissi, Italy.
³ Child and Adolescent Neuropsychiatry, Department of Medicine and Surgery and "SS. Giovanni di Dio e Ruggi d'Aragona - Schola Medica Salernitana" Hospital of the University of Salerno, Salerno, Italy.
⁴ Pediatric Neurology and Clinical Neurophysiology Unit, Department of Pediatrics, University of Padova, Italy.
⁵ Deparment of Pediatrics DPMSC, University of Udine, Udine, Italy.
⁶ Child and Adolescent Neuropsychiatry, Department of Pediatrics, University of Turin, Turin, Italy.
⁷ Department of Pediatrics, University of Chieti, Chieti, Italy.
⁸ Laboratory of Molecular Medicine and Genomics, Department of Medicine and Surgery, University of Salerno, Baronissi, Italy; Molecular Pathology and Medical Genomics, "SS. Giovanni di Dio e Ruggi d'Aragona - Schola Medica Salernitana" Hospital of the University of Salerno, Salerno, Italy.
⁹ Child and Adolescent Neuropsychiatry, Department of Medicine and Surgery and "SS. Giovanni di Dio e Ruggi d'Aragona - Schola Medica Salernitana" Hospital of the University of Salerno, Salerno, Italy. Electronic address: gcoppola@unisa.it.

PMID: 24315024
DOI: 10.1016/j.eplepsyres.2013.11.007

Abstract

Sequencing of the KCNT1, PLCB1, SCN1A and TBC1D24 loci was performed in six children with typical features of malignant migrating partial seizures of infancy (MMPSI), to verify the presence of potential disease-causing mutations, including those already reported to be associated with the disease. Sanger sequencing failed to identify in these genes the previously reported pathogenic mutations in these patients, while a comprehensive mutational scanning analysis of these four loci by targeted re-sequencing led to detection of both intronic and exonic new variants. Based on the current knowledge, the sequence variants identified here do not allow to predict functional phenotypes that might explain, at least in part, MMPSI symptoms.

Keywords: KCNT1; MMPSI; PLCB1; SCN1A; TBC1D24; Targeted re-sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carrier Proteins / genetics
Epilepsies, Partial / diagnosis*
Epilepsies, Partial / genetics*
Female
GTPase-Activating Proteins
Genetic Variation
Humans
Infant
Male
Membrane Proteins
Mutation / genetics*
NAV1.1 Voltage-Gated Sodium Channel / genetics
Nerve Tissue Proteins / genetics
Phenotype
Phospholipase C beta / genetics
Potassium Channels / genetics
Potassium Channels, Sodium-Activated
Sequence Deletion

Substances

Carrier Proteins
GTPase-Activating Proteins
KCNT1 protein, human
Membrane Proteins
NAV1.1 Voltage-Gated Sodium Channel
Nerve Tissue Proteins
Potassium Channels
Potassium Channels, Sodium-Activated
SCN1A protein, human
TBC1D24 protein, human
PLCB1 protein, human
Phospholipase C beta