Jablonka S, Rossoll W, Schrank B, Sendtner M
Klinische Forschergruppe, Neuroregeneration, Dept. of Neurology, University of Wuerzburg, Germany.
J Neurol. 2000 Mar;247 Suppl 1:I37-42. doi: 10.1007/s004150050555.
Childhood spinal muscular atrophy (SMA) is a common autosomal recessive disorder which is characterized by muscle weakness due to degeneration of motoneurons in the spinal cord and brainstem nuclei. Positional cloning strategies have revealed several gene candidates including the genes for the survival motoneuron (SMN) and the neuronal apoptosis inhibitory protein (NAIP). Both genes are duplicated on chromosome 5. Homozygous deletions/mutations of the telomeric SMN gene, which is expressed from both copies on human chromosome 5, are associated with the disease. Recent reports suggest involvement of the SMN protein in the formation of spliceosomal particles in the cytoplasm and in the regeneration of spliceosomes in the nucleus. These data put spinal muscular atrophy into a growing group of disorders of RNA metabolism which also include fragile-X syndrome and myotonic dystrophy. Relevance of these previous data for the pathogenesis of the disease are discussed in this review.
儿童脊髓性肌萎缩症（SMA）是一种常见的常染色体隐性疾病，其特征是由于脊髓和脑干核中的运动神经元退化而导致肌肉无力。定位克隆策略已揭示了几个候选基因，包括生存运动神经元（SMN）基因和神经元凋亡抑制蛋白（NAIP）基因。这两个基因在5号染色体上均有重复。端粒SMN基因在人类5号染色体的两个拷贝上均有表达，该基因的纯合缺失/突变与该病相关。最近的报道表明，SMN蛋白参与细胞质中剪接体颗粒的形成以及细胞核中剪接体的再生。这些数据使脊髓性肌萎缩症归入了一组不断增加的RNA代谢紊乱疾病，其中还包括脆性X综合征和强直性肌营养不良症。本综述讨论了这些先前数据与该疾病发病机制的相关性。
