Department of Neurology, University of California, San Francisco.
Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois3Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
JAMA Neurol. 2016 Dec 1;73(12):1485-1490. doi: 10.1001/jamaneurol.2016.3097.
The hereditary progressive ataxias comprise genetic disorders that affect the cerebellum and its connections. Even though these diseases historically have been among the first familial disorders of the nervous system to have been recognized, progress in the field has been challenging because of the large number of ataxic genetic syndromes, many of which overlap in their clinical features.
We have taken a historical approach to demonstrate how our knowledge of the genetic basis of ataxic disorders has come about by novel techniques in gene sequencing and bioinformatics. Furthermore, we show that the genes implicated in ataxia, although seemingly unrelated, appear to encode for proteins that interact with each other in connected functional modules.
It has taken approximately 150 years for neurologists to comprehensively unravel the genetic diversity of ataxias. There has been an explosion in our understanding of their molecular basis with the arrival of next-generation sequencing and computer-driven bioinformatics; this in turn has made hereditary ataxias an especially well-developed model group of diseases for gaining insights at a systems level into genes and cellular pathways that result in neurodegeneration.
遗传性进行性共济失调症包括影响小脑及其连接的遗传疾病。尽管这些疾病历来是神经系统中最早被识别的家族性疾病之一，但由于存在大量共济失调遗传综合征，其中许多在临床特征上重叠，该领域的进展一直具有挑战性。
我们采取了一种历史方法，通过基因测序和生物信息学的新技术来展示我们对共济失调疾病遗传基础的认识是如何产生的。此外，我们表明，虽然看似不相关，但与共济失调相关的基因似乎编码相互作用的蛋白质，这些蛋白质在连接的功能模块中相互作用。
神经学家花了大约 150 年的时间才全面揭示出共济失调症的遗传多样性。随着下一代测序和计算机驱动的生物信息学的出现，我们对其分子基础的理解有了爆炸式的增长；这反过来又使遗传性共济失调症成为一个特别发达的疾病模型组，可从系统水平深入了解导致神经退行性变的基因和细胞途径。
