Inwardly rectifying potassium channels (Kir) have been historically associated to several cardiovascular disorders. In particular, loss-of-function mutations in the Kir2.1 channel have been reported in cases affected by Andersen-Tawil syndrome while gain-of-function mutations in the same channel cause the short QT3 syndrome. Recently, a missense mutation in Kir2.1, as well as mutations in the Kir4.1, were reported to be involved in autism spectrum disorders (ASDs) suggesting a role of potassium channels in these diseases and introducing the idea of the existence of K+ channel ASDs. Here, we report the identification in an Italian affected family of a novel missense mutation (p.Phe58Ser) in the KCNJ2 gene detected in heterozygosity in a proband affected by autism and borderline for short QT syndrome type 3. The mutation is located in the N-terminal region of the gene coding for the Kir2.1 channel and in particular in a very conserved domain. In vitro assays demonstrated that this mutation results in an increase of the channel conductance and in its open probability. This gain-of-function of the protein is consistent with the autistic phenotype, which is normally associated to an altered neuronal excitability.

Binda, A., Rivolta, I., Villa, C., Chisci, E., Beghi, M., Cornaggia, C., et al. (2018). A novel KCNJ2 mutation identified in an autistic proband affects the single channel properties of Kir2.1. FRONTIERS IN CELLULAR NEUROSCIENCE, 12 [10.3389/fncel.2018.00076].

A novel KCNJ2 mutation identified in an autistic proband affects the single channel properties of Kir2.1

Binda, Anna
Primo
;
Rivolta, Ilaria
Secondo
;
Villa, Chiara;Chisci, Elisa;Beghi, Massimiliano;Cornaggia, Cesare M.;Giovannoni, Roberto
Penultimo
;
Combi, Romina
Ultimo
2018

Abstract

Inwardly rectifying potassium channels (Kir) have been historically associated to several cardiovascular disorders. In particular, loss-of-function mutations in the Kir2.1 channel have been reported in cases affected by Andersen-Tawil syndrome while gain-of-function mutations in the same channel cause the short QT3 syndrome. Recently, a missense mutation in Kir2.1, as well as mutations in the Kir4.1, were reported to be involved in autism spectrum disorders (ASDs) suggesting a role of potassium channels in these diseases and introducing the idea of the existence of K+ channel ASDs. Here, we report the identification in an Italian affected family of a novel missense mutation (p.Phe58Ser) in the KCNJ2 gene detected in heterozygosity in a proband affected by autism and borderline for short QT syndrome type 3. The mutation is located in the N-terminal region of the gene coding for the Kir2.1 channel and in particular in a very conserved domain. In vitro assays demonstrated that this mutation results in an increase of the channel conductance and in its open probability. This gain-of-function of the protein is consistent with the autistic phenotype, which is normally associated to an altered neuronal excitability.
Articolo in rivista - Articolo scientifico
Scientifica
Autism spectrum disorders; KCNJ2; Mutation; Patch clamp; Potassium channel; Single channel;
autism spectrum disorders, KCNJ2, potassium channel, mutation, patch clamp, single channel
English
Binda, A., Rivolta, I., Villa, C., Chisci, E., Beghi, M., Cornaggia, C., et al. (2018). A novel KCNJ2 mutation identified in an autistic proband affects the single channel properties of Kir2.1. FRONTIERS IN CELLULAR NEUROSCIENCE, 12 [10.3389/fncel.2018.00076].
Binda, A; Rivolta, I; Villa, C; Chisci, E; Beghi, M; Cornaggia, C; Giovannoni, R; Combi, R
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/192092
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