Molecular Neurosciences, Developmental Neuroscience, UCL Institute of Child Health, London, UK.
Developmental Neurosciences Programme, UCL GOS - Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK.
J Inherit Metab Dis. 2018 Nov;41(6):1077-1091. doi: 10.1007/s10545-018-0205-0. Epub 2018 Jun 13.
Movement disorders comprise a group of heterogeneous diseases with often complex clinical phenotypes. Overlapping symptoms and a lack of diagnostic biomarkers may hamper making a definitive diagnosis. Next-generation sequencing techniques have substantially contributed to unraveling genetic etiologies underlying movement disorders and thereby improved diagnoses. Defects in dopaminergic signaling in postsynaptic striatal medium spiny neurons are emerging as a pathogenic mechanism in a number of newly identified hyperkinetic movement disorders. Several of the causative genes encode components of the cAMP pathway, a critical postsynaptic signaling pathway in medium spiny neurons. Here, we review the clinical presentation, genetic findings, and disease mechanisms that characterize these genetic postsynaptic movement disorders.
运动障碍包括一组具有复杂临床表型的异质性疾病。重叠的症状和缺乏诊断生物标志物可能会阻碍明确诊断。下一代测序技术在揭示运动障碍的遗传病因方面做出了巨大贡献，从而提高了诊断水平。在许多新确定的运动过度性运动障碍中，突触后纹状体中间神经元中的多巴胺能信号传递缺陷正成为一种致病机制。一些致病基因编码 cAMP 途径的组成部分，cAMP 途径是中间神经元中一个关键的突触后信号传递途径。在这里，我们回顾了这些遗传性突触后运动障碍的临床表现、遗传发现和疾病机制。
