GRM1 中的显性突变导致脊髓小脑性共济失调 44 型。,American Journal of Human Genetics

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GRM1 中的显性突变导致脊髓小脑性共济失调 44 型。
American Journal of Human Genetics ( IF 8.1 ) Pub Date : 2017-09-07 00:00:00 , DOI: 10.1016/j.ajhg.2017.08.005
Lauren M Watson ₁ , Elizabeth Bamber ₁ , Ricardo Parolin Schnekenberg ₂ , Jonathan Williams ₃ , Conceição Bettencourt ₄ , Jennifer Lickiss ₅ , Sandeep Jayawant ₆ , Katherine Fawcett ₇ , Samuel Clokie ₅ , Yvonne Wallis ₅ , Penny Clouston ₃ , David Sims ₇ , Henry Houlden ₈ , Esther B E Becker ₁ , Andrea H Németh ₉

Affiliation

Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK.
Nuffield Department of Clinical Neurosciences, University of Oxford, 6th Floor West Wing, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Oxford Medical Genetics Laboratories, Churchill Hospital, Oxford OX3 7LE, UK.
Department of Molecular Neuroscience, Institute of Neurology, University College London, London WC1N 3BG, UK; Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, London WC1N 3BG, UK.
West Midlands Regional Genetics Laboratory, Birmingham Women's and Children's NHS Foundation Trust, Birmingham B15 2TG, UK.
Department of Paediatrics, Oxford University Hospitals NHS Trust, Oxford OX3 9DU, UK.
MRC Computational Genomics Analysis and Training Programme, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.
Department of Molecular Neuroscience, Institute of Neurology, University College London, London WC1N 3BG, UK.
Nuffield Department of Clinical Neurosciences, University of Oxford, 6th Floor West Wing, John Radcliffe Hospital, Oxford OX3 9DU, UK; Oxford Centre for Genomic Medicine, Oxford University Hospitals NHS Trust, Oxford OX3 7HE, UK.

代谢型谷氨酸受体 1 (mGluR1) 在哺乳动物中枢神经系统中大量表达，它调节细胞内钙稳态以响应兴奋性信号传导。在这里，我们描述了编码 mGluR1 的 GRM1 中的杂合显性突变，这些突变与不同的疾病表型相关：功能获得性错义突变，在两个不同的家族中与成人发病的小脑性共济失调有关，以及 ade novotruncation 突变导致显性-与青少年发病的共济失调和智力残疾有关的负面影响。至关重要的是，功能获得性突变可以在体外使用现有的 FDA 批准的药物硝唑尼特进行药理学调节，这表明了一种可能的治疗途径，目前无法用于治疗共济失调。

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更新日期：2017-09-21

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