Tesson Christelle, Koht Jeanette, Stevanin Giovanni
INSERM U1127, CNRS UMR7225, Sorbonne Universités, UPMC Univ Paris 06 UMR_S1127, EPHE, Institut du Cerveau et de la Moelle épinière, CHU Pitié-Salpêtrière, 47 bd de l'Hôpital, 75013, Paris, France.
Hum Genet. 2015 Jun;134(6):511-38. doi: 10.1007/s00439-015-1536-7. Epub 2015 Mar 11.
Hereditary spastic paraplegias (HSP) are rare neurodegenerative diseases sharing the degeneration of the corticospinal tracts as the main pathological characteristic. They are considered one of the most heterogeneous neurological disorders. All modes of inheritance have been described for the 84 different loci and 67 known causative genes implicated up to now. Recent advances in molecular genetics have revealed clinico-genetic heterogeneity of these disorders including their clinical and genetic overlap with other diseases of the nervous system. The systematic analysis of a large set of genes, including exome sequencing, is unmasking unusual phenotypes or inheritance modes associated with mutations in HSP genes and related genes involved in various neurological diseases. A new nosology may emerge after integration and understanding of these new data to replace the current classification. Collectively, functions of the known genes implicate the disturbance of intracellular membrane dynamics and trafficking as the consequence of alterations of cytoskeletal dynamics, lipid metabolism and organelle structures, which represent in fact a relatively small number of cellular processes that could help to find common curative approaches, which are still lacking.
遗传性痉挛性截瘫（HSP）是一类罕见的神经退行性疾病，其主要病理特征是皮质脊髓束发生退化。它们被认为是神经系统中异质性最高的疾病之一。目前已描述了所有的遗传模式，涉及84个不同的基因座和67个已知的致病基因。分子遗传学的最新进展揭示了这些疾病的临床-遗传异质性，包括它们与其他神经系统疾病的临床和遗传重叠。对大量基因进行系统分析，包括外显子组测序，正在揭示与HSP基因及参与各种神经系统疾病的相关基因中的突变有关的异常表型或遗传模式。在整合和理解这些新数据后，可能会出现一种新的疾病分类法来取代当前的分类。总体而言，已知基因的功能表明，细胞内膜动力学和运输的紊乱是细胞骨架动力学、脂质代谢和细胞器结构改变的结果，而这些实际上只是相对较少的一些细胞过程，它们有助于找到目前仍缺乏的共同治疗方法。
