497 research outputs found

    Novel loss-of-function variants expand ABCC9-related intellectual disability and myopathy syndrome

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    Loss-of-function mutation of ABCC9, the gene encoding the SUR2 subunit of ATP sensitive-potassium (KATP) channels, was recently associated with autosomal recessive ABCC9-related intellectual disability and myopathy syndrome (AIMS). Here we identify nine additional subjects, from seven unrelated families, harbouring different homozygous loss-of-function variants in ABCC9 and presenting with a conserved range of clinical features. All variants are predicted to result in severe truncations or in-frame deletions within SUR2, leading to the generation of non-functional SUR2-dependent KATP channels. Affected individuals show psychomotor delay and intellectual disability of variable severity, microcephaly, corpus callosum and white matter abnormalities, seizures, spasticity, short stature, muscle fatigability and weakness. Heterozygous parents do not show any conserved clinical pathology but report multiple incidences of intra-uterine fetal death, which were also observed in an eighth family included in this study. In vivo studies of abcc9 loss-of-function in zebrafish revealed an exacerbated motor response to pentylenetetrazole, a pro-convulsive drug, consistent with impaired neurodevelopment associated with an increased seizure susceptibility. Our findings define an ABCC9 loss-of-function-related phenotype, expanding the genotypic and phenotypic spectrum of AIMS and reveal novel human pathologies arising from KATP channel dysfunction

    Random sampling of colourings of sparse random graphs with a constant number of colours

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    In this work we present a simple and efficient algorithm which, with high probability, provides an almost uniform sample from the set of proper k-colourings on an instance of a sparse random graph G(n,d/n), where k=k(d) is a sufficiently large constant. Our algorithm is not based on the Markov Chain Monte Carlo method (M.C.M.C.). Instead, we provide a novel proof of correctness of our Algorithm that is based on interesting "spatial mixing" properties of colourings of G(n,d/n). Our result improves upon previous results (based on M.C.M.C.) that required a number of colours growing unboundedly with n.Comment: 30 pages 0 figures, uses fullpage.st

    Mononuclear and Dinuclear Manganese(II) Complexes from the Use of Methyl(2-pyridyl)ketone Oxime

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    The reactions of methyl(2-pyridyl)ketone oxime, (py)C(Me)NOH, with manganese(II) sulfate monohydrate have been investigated. The reaction between equimolar quantities of MnSO4 · H2O and (py)C(Me)NOH in H2O lead to the dinuclear complex [Mn2(SO4)2{(py)C(Me)NOH}4] · (py)C(Me)NOH, 1 · (py)C(Me)NOH, while employment of NaOMe as base affords the compound [Mn(HCO2)2{(py)C(Me)NOH}2] (2). The structures of both compounds have been determined by single crystal X-ray diffraction. In both complexes, the organic ligand chelates through its nitrogen atoms. The IR data are discussed in terms of the nature of bonding and the structures of the two complexes
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