University of California Irvine School of Medicine, Irvine, CA 92697, USA ; Neuromuscular Diseases Research Unit, Laboratory of Neurogenetics, NIA, NIH, Bethesda, MD 20892, USA.
Neuromuscular Diseases Research Unit, Laboratory of Neurogenetics, NIA, NIH, Bethesda, MD 20892, USA.
Alzheimers Res Ther. 2012 Jul 26;4(4):30. doi: 10.1186/alzrt133. eCollection 2012.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized clinically by rapidly progressive paralysis leading ultimately to death from respiratory failure. It is now recognized that ALS and frontotemporal lobar degeneration (FTLD) form a clinical spectrum of disease with overlapping clinical, pathological and genetic features. This past year, the genetic causes of ALS have expanded to include mutations in the genes OPTN, VCP, and UBQLN2, and the hexanucleotide repeat expansion in C9ORF72. The C9ORF72 repeat expansion solidifies the notion that ALS and FTLD are phenotypic variations of a disease spectrum with a common molecular etiology. Furthermore, the C9ORF72 expansion is the genetic cause of a substantial portion of apparently sporadic ALS and FTLD cases, showing that genetics plays a clear role in sporadic disease. Here we describe the progress made in the genetics of ALS and FTLD, including a detailed look at how new insights brought about by C9ORF72 have both broadened and unified current concepts in neurodegeneration.
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，临床上表现为迅速进展的瘫痪，最终导致呼吸衰竭死亡。现在已经认识到，肌萎缩侧索硬化症和额颞叶变性（FTLD）形成了一种具有重叠临床、病理和遗传特征的疾病谱。在过去的一年中，ALS 的遗传原因已经扩展到包括 OPTN、VCP 和 UBQLN2 基因的突变，以及 C9ORF72 中的六核苷酸重复扩展。C9ORF72 重复扩展巩固了这样一种观点，即肌萎缩侧索硬化症和额颞叶变性是一种疾病谱的表型变异，具有共同的分子病因。此外，C9ORF72 扩展是大量明显散发性 ALS 和 FTLD 病例的遗传原因，表明遗传在散发性疾病中起着明确的作用。在这里，我们描述了肌萎缩侧索硬化症和额颞叶变性遗传学方面的进展，包括详细探讨了 C9ORF72 带来的新见解如何既拓宽又统一了神经退行性变的现有概念。
