A Recurrent Mutation in KCNA2 as a Novel Cause of Hereditary Spastic Paraplegia and Ataxia

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Helbig , K L , Hedrich , U B S , Shinde , D N , Krey , I , Teichmann , A-C , Hentschel , J , Schubert , J , Chamberlin , A C , Huether , R , Lu , H-M , Alcaraz , W A , Tang , S , Jungbluth , C , Dugan , S L , Vainionpaa , L , Karle , K N , Synofzik , M , Schols , L , Schule , R , Lehesjoki , A-E , Helbig , I , Lerche , H & Lemke , J R 2016 , ' A Recurrent Mutation in KCNA2 as a Novel Cause of Hereditary Spastic Paraplegia and Ataxia ' , Annals of Neurology , vol. 80 , no. 4 , pp. 638-642 . https://doi.org/10.1002/ana.24762

Title: A Recurrent Mutation in KCNA2 as a Novel Cause of Hereditary Spastic Paraplegia and Ataxia
Author: 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.; Vainionpaa, Leena; Karle, Kathrin N.; Synofzik, Matthis; Schols, Ludger; Schule, Rebecca; Lehesjoki, Anna-Elina; Helbig, Ingo; Lerche, Holger; Lemke, Johannes R.
Contributor: University of Helsinki, Neuroscience Center
Date: 2016-10
Language: eng
Number of pages: 5
Belongs to series: Annals of Neurology
ISSN: 0364-5134
URI: http://hdl.handle.net/10138/172635
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, K(V)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 KV1.2 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.
Subject: SHAKER K+ CHANNEL
EPILEPTIC ENCEPHALOPATHY
MOLECULAR-MECHANISMS
VOLTAGE SENSOR
KV1.2
CEREBELLAR
DISORDERS
GENETICS
SEGMENT
3112 Neurosciences
3124 Neurology and psychiatry
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