Journal article

Dominant KCNA2 mutation causes episodic ataxia and pharmacoresponsive epilepsy

Mark A Corbett, Susannah T Bellows, Melody Li, Renee Carroll, Silvana Micallef, Gemma L Carvill, Candace T Myers, Katherine B Howell, Snezana Maljevic, Holger Lerche, Elena V Gazina, Heather C Mefford, Melanie Bahlo, Samuel F Berkovic, Steven Petrou, Ingrid E Scheffer, Jozef Gecz



OBJECTIVE: To identify the genetic basis of a family segregating episodic ataxia, infantile seizures, and heterogeneous epilepsies and to study the phenotypic spectrum of KCNA2 mutations. METHODS: A family with 7 affected individuals over 3 generations underwent detailed phenotyping. Whole genome sequencing was performed on a mildly affected grandmother and her grandson with epileptic encephalopathy (EE). Segregating variants were filtered and prioritized based on functional annotations. The effects of the mutation on channel function were analyzed in vitro by voltage clamp assay and in silico by molecular modeling. KCNA2 was sequenced in 35 probands with heterogeneous phenotypes. RESULTS: T..

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Awarded by NHMRC program

Awarded by NHMRC Research Fellowships

Awarded by NHMRC Practitioner Fellowship

Funding Acknowledgements

This project was supported by NHMRC program grants 628952 (S.T.B., S.F.B., J.G., I.E.S., S.P.) and 1054618 (M.B.), NHMRC Research Fellowships 1041920 (J.G.) and 1002098 (M.B.), NHMRC Practitioner Fellowship 1104831 (I.E.S.), WCH foundation MS McLeod research fellowship (M.A.C.), Victorian Government's Operational Infrastructure Support Program, and Australian Government NHMRC IRIISS.