Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
J Neurol Sci. 2011 Sep 15;308(1-2):83-7. doi: 10.1016/j.jns.2011.06.002. Epub 2011 Jun 25.
Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by programmed motoneuron death. The survival motor neuron 1 (SMN1) gene is an SMA-determining gene and SMN2 represents an SMA-modifying gene. Here, we applied capillary electrophoresis to quantify the SMN gene dosage in 163 normal individuals, 94 SMA patients and 138 of their parents. We further quantified exons 7 and 8 in SMN1 and SMN2. We found that the SMA patients carried the highest SMN2 copies, which was inversely correlated with disease severity among its three subtypes. Increased SMN1 was significantly associated with decreased SMN2 in the normal group. We also observed that parents of type I SMA patients had significantly fewer SMN2 copies than those of types II and III patients. The hybrid SMN genes were detected in two normal individuals and one patient and her mother. These results imply that increased SMN2 copies in SMA patient group might be derived from SMN1-to-SMN2 conversion, whereas the trend that normal individuals with higher SMN1 copies simultaneously carry fewer SMN2 copies suggested a reverse conversion, SMN2-to-SMN1. Together with the identification of hybrid SMN genes, our data provided additional evidence to support that SMN1 and SMN2 gene loci are interchangeable between population groups.
脊髓性肌萎缩症（SMA）是一种神经退行性疾病，其特征是运动神经元进行性死亡。运动神经元存活 1 号（SMN1）基因是 SMA 的决定性基因，SMN2 则是 SMA 的修饰基因。在此，我们应用毛细管电泳技术对 163 名正常个体、94 名 SMA 患者及其 138 位家长的 SMN 基因剂量进行了定量分析。我们还对 SMN1 和 SMN2 的外显子 7 和 8 进行了定量分析。结果发现，SMA 患者携带的 SMN2 拷贝数最高，且与三个亚型的疾病严重程度呈负相关。正常组中 SMN1 的增加与 SMN2 的减少显著相关。我们还观察到，I 型 SMA 患者的父母携带的 SMN2 拷贝数明显少于 II 型和 III 型患者的父母。在两名正常个体和一名患者及其母亲中检测到了杂合 SMN 基因。这些结果表明，SMA 患者组中 SMN2 拷贝数的增加可能源于 SMN1 到 SMN2 的转换，而正常个体中 SMN1 拷贝数较高的同时携带较少的 SMN2 拷贝的趋势则表明存在反向转换，即 SMN2 到 SMN1。结合对杂合 SMN 基因的鉴定，我们的数据提供了更多证据，支持了 SMN1 和 SMN2 基因座在人群中可相互转换的观点。
