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A recurrent mutation in KCNA2 as a novel cause of hereditary spastic paraplegia and ataxia.

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.

SUBMITTER: Helbig KL

PROVIDER: S-EPMC5129488 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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A recurrent mutation in KCNA2 as a novel cause of hereditary spastic paraplegia and ataxia.

Helbig Katherine L KL Hedrich Ulrike B S UB Shinde Deepali N DN Krey Ilona I Teichmann Anne-Christin AC Hentschel Julia J Schubert Julian J Chamberlin Adam C AC Huether Robert R Lu Hsiao-Mei HM Alcaraz Wendy A WA Tang Sha S Jungbluth Chelsy C Dugan Sarah L SL Vainionpää Leena L Karle Kathrin N KN Synofzik Matthis M Schöls Ludger L Schüle Rebecca R Lehesjoki Anna-Elina AE Helbig Ingo I Lerche Holger H Lemke Johannes R JR

Annals of neurology 20160909 4

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 recordin ...[more]

PMID: 27543892

Dataset Information

A recurrent mutation in KCNA2 as a novel cause of hereditary spastic paraplegia and ataxia.

Publications

A recurrent mutation in KCNA2 as a novel cause of hereditary spastic paraplegia and ataxia.

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