Two mutations in the nicotinic acetylcholine receptor subunit A4 (CHRNA4) in a family with autosomal dominant sleep-related hypermotor epilepsy.
Langenbruch L1, Biskup S2, Young P3, Dräger B1, Möddel G1.
Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster.
CeGaT GmbH, Tübingen, Praxis für Humangenetik, Tübingen.
Department of Neurology, Medical Park Bad Feilnbach, Bad Feilnbach, Germany.
Sleep-related hypermotor epilepsy, or nocturnal frontal lobe epilepsy, as it was formerly called, is a focal epilepsy with mostly sleep-related seizures of hypermotor, tonic or dystonic semiology. Sleep-related hypermotor epilepsy may be attributed to a monogenetic cause with autosomal dominant inheritance. Mutations are described in different genes, including the genes for three subunits of the nicotinic acetylcholine receptor. We present a family with members over four generations exhibiting sleep-related hypermotor epilepsy. Genetic testing was available for three members from three generations, and revealed two variants in the alpha-4 subunit of the nicotinic acetylcholine receptor (one of them being novel) which are likely to be disease-causing. As these mutations were identified in cis configuration (on the same allele), we do not know whether one of the variants alone or a combination of the two is responsible for the pathogenicity.