A variant of KCC2 from patients with febrile seizures impairs neuronal Cl− extrusion and dendritic spine formation. (25th March 2014)

• Record Type: Journal Article
• Authors: Puskarjov, Martin; Seja, Patricia; Heron, Sarah E; Williams, Tristiana C; Ahmad, Faraz; Iona, Xenia; Oliver, Karen L; Grinton, Bronwyn E; Vutskits, Laszlo; Scheffer, Ingrid E; Petrou, Steven; Blaesse, Peter; Dibbens, Leanne M; Berkovic, Samuel F; Kaila, Kai
• Is Part Of: EMBO reports. Volume 15:Number 6(2014:Jun.)
• Page Start: 723
• Page End: 729
• Publication Date: 2014-03-25
• Subjects: Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.1002/embr.201438749
• Languages: English
• ISSNs: 1469-221X

Abstract

<abstract abstract-type="synopsis" xml:lang="en" id="embr201438749-abs-0002"> <title>Synopsis</title> <p> <boxed-text content-type="graphic" id="embr201438749-blkfxd-0001" position="anchor" orientation="portrait"> <graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pghctmtvrv" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /> </boxed-text> </p> <p>A missense mutation of the K‐Cl co‐transporter KCC2, identified in patients with febrile seizures, leads to defects in neuronal Cl⁻ extrusion and dendritic spine formation <italic>in vivo</italic> and in cultured cells.</p> <p> <list id="embr201438749-list-0001" list-type="bullet"> <list-item> <p>A rare <italic>SLC12A5</italic> variant with an arginine‐to‐histidine substitution at position 952 in the KCC2b isoform is identified in an Australian family with early childhood onset of febrile seizures.</p> </list-item> <list-item> <p>Expression of the KCC2‐R952H variant leads to reduced Cl⁻ extrusion, cortical dendritic spine formation and surface expression of the KCC2b protein.</p> </list-item> <list-item> <p>The significant functional deficits taken together with the low genetic tolerance of <italic>SLC12A5</italic> are consistent with a role for KCC2‐R952H as a susceptibility gene in febrile seizures.</p> </list-item> </list> </p> </abstract>