22 February 2021
Genetic mutations behind rare epileptic condition
Published online 9 April 2013
Mutations in a gene that is crucial for generating nervous impulses have been identified as the likely cause of a rare condition called cortical myoclonic tremor with epilepsy1.
The discovery, by a team of researchers led by Elizabeth Stogmann of the University of Vienna, including scientists from Ain Shams University in Cairo, could lead to a better understanding of more common forms of epilepsy.
Cortical myoclonic tremor is characterised by epileptic seizures and mild, irregular tremors of the head and arms. It is inherited in an autosomal recessive manner in this family, or by the inheritance of two mutated copies of the same gene.
Stogmann and her colleagues studied a consanguineous Egyptian family in which five siblings are affected by the condition. By comparing their genomes with more than 500 healthy controls from Austria and North Africa using genome-wide linkage analysis, the researchers identified mutations in the CNTN2 gene present in the affected siblings but not in the controls or other epileptic patients.
CNTN2 encodes an adhesion molecule called contactin 2, which helps maintain potassium channels at the correct places along nerve fibres. Potassium channels are critical for generating nerve impulses, making cells return to their resting state so that they can fire again.
Epilepsy takes different forms, but all involve overly excited neurons that cause excess electrical activity underlying the seizures. "The crucial role of CNTN2 in neuronal excitability makes this gene a plausible candidate for cortical myoclonic tremor and epilepsy," says Stogmann. "Future studies may prove the role of CNTN2 in a broader spectrum of epilepsy patients."