A recurrent mutation in KCNA2 as a novel cause of hereditary spastic paraplegia and ataxia. Issue 4 (9th September 2016)

• Record Type: Journal Article
• Authors: Helbig, Katherine L.; Hedrich, Ulrike B.S.; Shinde, Deepali N.; Krey, Ilona; Teichmann, Anne‐Christin; Hentschel, Julia; Schubert, Julian; Chamberlin, Adam C.; Huether, Robert; Lu, Hsiao‐Mei; Alcaraz, Wendy A.; Tang, Sha; Jungbluth, Chelsy; Dugan, Sarah L.; Vainionpää, Leena; Karle, Kathrin N.; Synofzik, Matthis; Schöls, Ludger; Schüle, Rebecca; Lehesjoki, Anna‐Elina; Helbig, Ingo; Lerche, Holger; Lemke, Johannes R.
• Is Part Of: Annals of neurology. Volume 80:Issue 4(2016:Oct.)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2016-09-09
• Subjects: Neurology -- Periodicals; Pediatric neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; 616.8
• DOI: 10.1002/ana.24762
• Languages: English
• ISSNs: 0364-5134

Abstract

Abstract : The hereditary spastic paraplegias (HSPs) are heterogeneous neurodegenerative disorders with over 50 known causative genes. We identified a recurrent mutation in KCNA2 (c.881G>A, p.R294H), encoding the voltage‐gated K + ‐channel, KV 1.2, in two unrelated families with HSP, intellectual disability (ID), and ataxia. Follow‐up analysis of > 2, 000 patients with various neurological phenotypes identified a de novo p.R294H mutation in a proband with ataxia and ID. Two‐electrode voltage‐clamp recordings of Xenopus laevis oocytes expressing mutant KV 1.2 channels showed loss of function with a dominant‐negative effect. Our findings highlight the phenotypic spectrum of a recurrent KCNA2 mutation, implicating ion channel dysfunction as a novel HSP disease mechanism. Ann Neurol 2016