J Med Genet. 2010 Sep;47(9):640-2. doi: 10.1136/jmg.2010.079004. Epub 2010 Jun 24.
Homozygous mutations of the telomeric SMN1 gene lead to degeneration of motor neurons causing spinal muscular atrophy (SMA). A highly similar centromeric gene (SMN2) can only partially compensate for SMN1 deficiency. The c.859G>C variant in SMN2 has been recently reported as a positive disease modifier. We identified the variant in 10 unrelated chronic SMA patients with a wide spectrum of phenotypes ranging from type II patients who can only sit to adult walkers. Haplotype analysis strongly suggests that the variant originated from a common ancestor. Our results confirm that the c.859G>C variant is a milder SMN2 allele and predict a direct correlation between SMN activity and phenotypic severity.
纯合的端粒 SMN1 基因突变会导致运动神经元退化，从而引起脊髓性肌萎缩症（SMA）。一个高度相似的着丝粒基因（SMN2）只能部分补偿 SMN1 的缺乏。最近有报道称，SMN2 中的 c.859G>C 变体是一种积极的疾病修饰因子。我们在 10 名无关联的慢性 SMA 患者中发现了这种变体，这些患者的表型范围广泛，从只能坐的 II 型患者到成年步行者都有。单体型分析强烈表明该变体源自一个共同的祖先。我们的结果证实，c.859G>C 变体是一个较温和的 SMN2 等位基因，并预测 SMN 活性与表型严重程度之间存在直接相关性。
