The genetics of spinal muscular atrophies
The genetics of spinal muscular atrophies
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DOI：
10.1097/wco.0b013e32833e1765
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发表时间：
2010-10-01
影响因子：
4.8
通讯作者：
Sumner, Charlotte J.
中科院分区：
文献类型：
--
作者：
Wee, Claribel D.;Kong, Lingling;Sumner, Charlotte J.
综述目的本文综述了脊髓性肌萎缩症（SMA）的临床、遗传和治疗进展，SMA是一种以运动神经元缺失和肌无力为特征的遗传性疾病，在确定至少16种不同形式SMA的临床和遗传特征方面取得了进展。在过去的十年中，已经确定了与这些疾病中的14种相关的基因，其中包括去年的四种：TRPV 4，ATP 7A，VRK 1和HSPB 3。现在，许多SMA都可以进行基因检测，提供重要的诊断和预后信息。SMA的细胞和动物模型已被用于进一步了解SMA相关基因的突变如何导致运动神经元功能障碍和丧失，SMA相关基因编码参与转录调控、RNA加工和细胞骨架动力学等多种功能的蛋白质。在过去的一年中，也有显着的进展，近端SMA的临床前治疗的发展，使用基因治疗，反义寡核苷酸，和small molecule.SummaryThe进步的临床和遗传特性的不同形式的SMA的临床评价和管理的患者有重要的意义。多种新型SMA致病基因的发现将有助于我们更好地理解运动神经元疾病的生物学，并可能为治疗药物的开发提供新的靶点。
Purpose of reviewThis article reviews clinical, genetic, and therapeutic advances in spinal muscular atrophies (SMAs), inherited disorders characterized by motor neuron loss and muscle weakness.Recent findingsThere has been progress in defining the clinical and genetic features of at least 16 distinct forms of SMA. The genes associated with 14 of these disorders have been identified in the last decade, including four within the last year: TRPV4, ATP7A, VRK1, and HSPB3. Genetic testing is now available for many SMAs, providing important diagnostic and prognostic information. Cell and animal models of SMAs have been used to further understand how mutations in SMA-associated genes, which code for proteins involved in diverse functions such as transcriptional regulation, RNA processing, and cytoskeletal dynamics, lead to motor neuron dysfunction and loss. In the last year, there has also been remarkable progress in preclinical therapeutics development for proximal SMA using gene therapy, antisense oligonucleotides, and small molecules.SummaryThe advances in the clinical and genetic characterization of different forms of SMAs have important implications for clinical evaluation and management of patients. The identification of multiple, novel SMA-causing genes will lead to an improved understanding of motor neuron disease biology and may provide novel targets for therapeutics development.