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- Title
A recurrent mutation in KCNA2 as a novel cause of hereditary spastic paraplegia and ataxia.
- 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
- 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.
- Publication
Annals of Neurology, 2016, Vol 80, Issue 4, pn/a
- ISSN
0364-5134
- Publication type
journal article
- DOI
10.1002/ana.24762