Zhang Wenhui, Cao Yanyan, Song Fang, Qu Yujin, Bai Jinli, Jin Yuwei, Wang Hong
Department of Medical Genetics, Capital Institute of Pediatrics, Beijing 100020, China.
Department of Medical Genetics, Capital Institute of Pediatrics, Beijing 100020, China. Email:
Zhonghua Yi Xue Za Zhi. 2015 Feb 10;95(6):430-4.
To explore the diversity of mutations in survival motor neuron gene 1 (SMN1) by analyzing seven cases of partial deletion of SMN1 gene.
Seven patients suspected spinal muscular atrophy (SMA) were recruited from 2011 to 2013. Multiplex ligation-dependent probe amplification (MLPA) for genetic testing of SMA was based on the commercially available SALSA MLPA kit P021-A2. Then the data were analyzed by the software Coffalyser.Negative control samples were chosen with two copies of SMN1 and SMN2. Positive control samples were chosen with zero copies of SMN1 and two copies of SMN2. According to the product description (www.mlpa.com): for exon 7 and 8 of SMN1 and SMN2: a ratio of <0.7 indicates 1 copy, a ratio of 0.7-1.3 2 copies, a ratio of 1.3-1.7 3 copies and a ratio of 1.7-2.3 4 copies. For exon 1, 4, 6, 8 of SMN gene (SMN1+SMN2): a ratio <0.4 indicates 1 copy, a ratio of 4.0-0.6 2 copies, a ratio of 0.7-0.9 3 copies and a ratio of 0.9-1.1 4 copies. All samples were analyzed in duplicate.
Using MLPA for clinical diagnostics, two types of partial deletions of SMN1were identified in 7 patients.Since exon 8 is not translated and has no effect on the function of SMN protein, exons 1, 4, 6, 7 were targeted.One had an isolated deletion of exon 7 while the other ones were caused by the deletions of exon 1, 4 and 7. These mutations were not detected by conventional diagnostic methods. Both types of partial deletions of SMN1 gene contained a deletion of exon 7.
Two types of partial deletions of SMN1 gene indicate that the structure of SMN gene is unstable leading to a variety of mutation forms. But the major cause of SMA lies in a deletion of exon 7 of SMN1 gene.
通过分析7例生存运动神经元基因1（SMN1）部分缺失病例，探讨SMN1基因突变的多样性。
2011年至2013年招募了7例疑似脊髓性肌萎缩症（SMA）患者。基于市售的SALSA MLPA试剂盒P021 - A2进行多重连接依赖探针扩增（MLPA）用于SMA的基因检测。然后用Coffalyser软件分析数据。阴性对照样本选择为有两份SMN1和SMN2。阳性对照样本选择为零份SMN1和两份SMN2。根据产品说明书（www.mlpa.com）：对于SMN1和SMN2的外显子7和8：比值<0.7表示1份，比值0.7 - 1.3表示2份，比值1.3 - 1.7表示3份，比值1.7 - 2.3表示4份。对于SMN基因（SMN1 + SMN2）的外显子1、4、6、8：比值<0.4表示1份，比值4.0 - 0.6表示2份，比值0.7 - 0.9表示3份，比值0.9 - 1.1表示4份。所有样本均进行重复分析。
采用MLPA进行临床诊断，在7例患者中鉴定出两种类型的SMN1部分缺失。由于外显子8不参与翻译且对SMN蛋白功能无影响，因此以外显子1、4、6、7为靶点。1例患者为外显子7的孤立缺失，其他患者为外显子1、4和7的缺失。这些突变用传统诊断方法未检测到。两种类型的SMN1基因部分缺失均包含外显子7的缺失。
SMN1基因的两种类型部分缺失表明SMN基因结构不稳定，导致多种突变形式。但SMA的主要病因在于SMN1基因外显子7的缺失。
