First mutation in the voltage-gated NaV1.1 subunit gene SCN1A with co-occurring familial hemiplegic migraine and epilepsy

Authors


Arn MJM van den Maagdenberg, PhD, Department of Human Genetics, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, the Netherlands. Tel. + 31-71-526-9460, fax + 31-71-526-8285, e-mail maagdenberg@lumc.nl

Abstract

Almost all mutations in the SCN1A gene, encoding the α1 subunit of neuronal voltage-gated NaV1.1 sodium channels, are associated with severe childhood epilepsy. Recently, two mutations were identified in patients with pure familial hemiplegic migraine (FHM). Here, we identified a novel SCN1A L263V mutation in a Portuguese family with partly co-segregating hemiplegic migraine and epilepsy. The L263V mutation segregated in five FHM patients, three of whom also had epileptic attacks, occurring independently from their hemiplegic migraine attacks. L263V is the first SCN1A mutation associated with FHM and co-occurring epilepsy in multiple mutation carriers, and is the clearest molecular link between migraine and epilepsy thus far. The results extend the clinical spectrum associated with SCN1A mutations and further strengthen the molecular evidence that FHM and epilepsy share, at least in part, similar molecular pathways.

Ancillary