In:
Annals of Neurology, Wiley, Vol. 80, No. 4 ( 2016-10)
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 K V 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
Type of Medium:
Online Resource
ISSN:
0364-5134
,
1531-8249
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
2037912-2
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