Genetic and functional characterisation of the P/Q calcium channel in episodic ataxia with epilepsy (pages 1905–1913)
Sanjeev Rajakulendran, Tracey D. Graves, Robyn W. Labrum, Dimitrios Kotzadimitriou, Louise Eunson, Mary B. Davis, Rosalyn Davies, Nicholas W. Wood, Dimitri M. Kullmann, Michael G. Hanna and Stephanie Schorge
Article first published online: 28 MAY 2010 | DOI: 10.1113/jphysiol.2009.186437
Rare inherited mutations of the CACNA1A gene cause bouts of incoordination (episodic ataxia), and sometimes epilepsy. CACNA1A encodes a protein that allows calcium ions to travel through the membranes of neurons. We have studied the sequence of CACNA1A in people with episodic ataxia and epilepsy. We found that, in addition to rare mutations, genetic changes that are present in the general population (polymorphisms) occur in these patients. A common feature of the over-represented polymorphisms is that they subtly reduce the flow of calcium ions through the membrane. Our results show that by carefully measuring the effects of common polymorphisms, it is possible to detect genetic factors that contribute to the susceptibility to neurological diseases characterised by altered neuronal excitability.