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De novo KCNA1 variants in the PVP motif cause infantile epileptic encephalopathy and cognitive impairment similar to recurrent KCNA2 variants
Washington Univ, Dept Neurol, 660 S Euclid Ave,Campus Box 8111, St Louis, MO 63110 USA.
Washington Univ, Dept Neurol, 660 S Euclid Ave,Campus Box 8111, St Louis, MO 63110 USA.
Univ Florence, Anna Meyer Childrens Hosp, Florence, Italy.
Univ Florence, Anna Meyer Childrens Hosp, Florence, Italy.
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2018 (English)In: American Journal of Medical Genetics. Part A, ISSN 1552-4825, E-ISSN 1552-4833, Vol. 176, no 8, p. 1748-1752Article in journal (Refereed) Published
Abstract [en]

Derangements in voltage-gated potassium channel function are responsible for a range of paroxysmal neurologic disorders. Pathogenic variants in the KCNA1 gene, which encodes the voltage-gated potassium channel Kv1.1, are responsible for Episodic Ataxia Type 1 (EA1). Patients with EA1 have an increased incidence of epilepsy, but KCNA1 variants have not been described in epileptic encephalopathy. Here, we describe four patients with infantile-onset epilepsy and cognitive impairment who harbor de novo KCNA1 variants located within the Kv-specific Pro-Val-Pro (PVP) motif which is essential for channel gating. The first two patients have KCNA1 variants resulting in (p.Pro405Ser) and (p.Pro405Leu), respectively, and a set of identical twins has a variant affecting a nearby residue (p.Pro403Ser). Notably, recurrent de novo variants in the paralogous PVP motif of KCNA2 have previously been shown to abolish channel function and also cause early-onset epileptic encephalopathy. Importantly, this report extends the range of phenotypes associated with KCNA1 variants to include epileptic encephalopathy when the PVP motif is involved.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018. Vol. 176, no 8, p. 1748-1752
Keywords [en]
cognitive impairment, epilepsy, epileptic encephalopathy, infantile epilepsy, KCNA1, KCNA2, potassium channel mutation, PVP motif
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:uu:diva-363992DOI: 10.1002/ajmg.a.38840ISI: 000442489700010PubMedID: 30055040OAI: oai:DiVA.org:uu-363992DiVA, id: diva2:1260904
Available from: 2018-11-05 Created: 2018-11-05 Last updated: 2018-11-05Bibliographically approved

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Thuresson, Ann-Charlotte

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