11 research outputs found

    A Novel KCNJ2 Mutation Identified in an Autistic Proband Affects the Single Channel Properties of Kir2.1

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    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

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    <p>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<sup>+</sup> 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.</p

    Psychiatric events in epilepsy

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    Psychiatric events are thought to be more frequent in people with epileptic seizures than in the general population. However, inter-ictal psychiatric events attributable to epilepsy remain controversial. The aim of the present study was to evaluate the occurrence of psychiatric events in a population of fairly unselected patients with epilepsy and in the general population, and the correlation between psychiatric complaints and selected demographic and disease characteristics. The survey was part of a multicentre prospective cohort study of everyday life risks conducted in eight European countries and comparing referral children and adults with epilepsy referred to secondary/tertiary centers to age- and sex-matched non-epileptic controls. Nine hundred and fifty-one patients with epilepsy and 909 controls were studied. Each patient and his/her control received a diary to record any accident or illness, with severity, circumstances, causes, consequences, and (for the cases) the possible relation to a seizure. The follow-up period ranged between 1 and 2 years. Fifty-eight psychiatric events occurred in 25 patients (2.6%) and 88 in 19 controls (2.1%). Housewives (9.3%) and unemployed persons (4.1%) were mostly affected. No correlation was found between psychiatric events, demographic and disease characteristics. Our results suggest that people with epilepsy if unselected are not at higher risk for psychiatric disorders than the general population. © 2007 British Epilepsy Association

    Credit Rating Agencies

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    Problems Inherent in the Compensation and Business Models of Credit Rating Agencies.

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