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01-03-2020 | Juvenile Myoclonic Epilepsy | Original Article

Whole exome sequencing identifies a novel SCN1A mutation in genetic (idiopathic) generalized epilepsy and juvenile myoclonic epilepsy subtypes

Authors: Chung-Kin Chan, Joyce Siew-Yong Low, Kheng-Seang Lim, Siew-Kee Low, Chong-Tin Tan, Ching-Ching Ng

Published in: Neurological Sciences | Issue 3/2020

Abstract

Introduction

Genetic (idiopathic) generalized epilepsy (GGE) is a common form of epilepsy characterized by unknown aetiology and a presence of genetic component in its predisposition.

Methods

To understand the genetic factor in a family with GGE, we performed whole exome sequencing (WES) on a trio of a juvenile myoclonic epilepsy/febrile seizure (JME/FS) proband with JME/FS mother and healthy father. Sanger sequencing was carried out for validation of WES results and variant detection in other family members.

Results

Predictably damaging variant found in affected proband and mother but absent in healthy father in SCN1A gene was found to be associated with generalized epilepsy and febrile seizure. The novel non-synonymous substitution (c.5753C>T, p.S1918F) in SCN1A was found in all family members with GGE, of which 4/8 were JME subtypes, and/or febrile seizure, while 3 healthy family member controls did not have the mutation. This mutation was also absent in 41 GGE patients and 414 healthy Malaysian Chinese controls.

Conclusion

The mutation is likely to affect interaction between the sodium channel and calmodulin and subsequently interrupt calmodulin-dependent modulation of the channel.

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Title: Whole exome sequencing identifies a novel SCN1A mutation in genetic (idiopathic) generalized epilepsy and juvenile myoclonic epilepsy subtypes
Authors: Chung-Kin Chan
Joyce Siew-Yong Low
Kheng-Seang Lim
Siew-Kee Low
Chong-Tin Tan
Ching-Ching Ng
Publication date: 01-03-2020
Publisher: Springer International Publishing
Keywords: Juvenile Myoclonic Epilepsy
Febrile Seizure
Electroencephalography
Epilepsy
Published in: Neurological Sciences / Issue 3/2020
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-019-04122-9

At a glance: The STEP trials

Springer Medicine

Whole exome sequencing identifies a novel SCN1A mutation in genetic (idiopathic) generalized epilepsy and juvenile myoclonic epilepsy subtypes

Abstract

Introduction

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

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