脊髓性肌萎缩症患儿SMN1和SMN2基因拷贝数与临床表型的相关性分析

目的 对脊髓性肌萎缩症（SMA）患儿的运动神经元存活基因1（SMN1）和SMN2拷贝数与临床表型之间的关系进行分析，提高对SMA患儿的早期诊断和临床干预水平。方法 选取45例SMA患儿，应用多重连接依赖性探针扩增技术对SMN1和SMN2基因拷贝数进行检测，分析SMN基因拷贝数同临床表型之间的关系。结果 45例SMA患儿中，SMN1第7和8外显子纯合缺失者为42例，占93%（42/45）；仅有第7外显子缺失者为3例，占7%（3/45）。SMA不同临床分型和SMN1基因第7、8外显子缺失类型间无相关性（P > 0.05）；SMA患儿和健康儿童的SMN2基因拷贝数分布差异有统计学意义（P < 0.05），前者以2和3拷贝者居多，后者以1和2拷贝者居多；不同SMA临床分型间SMN2拷贝数分布差异有统计学意义（P < 0.05），SMN2基因为2拷贝者发病年龄明显小于3和4拷贝者。Ⅰ型SMA患儿中SMN2拷贝数以2或3拷贝者居多，Ⅱ型以3拷贝者居多，Ⅲ型以3或4拷贝者居多。随着SMN2拷贝数增加，患儿发病年龄越大，保有的运动功能和临床结局越好，SMN2基因拷贝数同临床结局间的关系存在显著性差异（P < 0.05）。结论 SMN2基因通过剂量补偿效应减轻SMA疾病严重程度，SMN2拷贝数同SMA临床表型具有相关性，可将其作为预测疾病严重程度的依据之一。

Association of copy number of SMN1 and SMN2 with clinical phenotypes in children with spinal muscular atrophy

Objective To study the association of copy number of SMN1 and SMN2 with clinical phenotypes in children with spinal muscular atrophy (SMA). Methods A total of 45 children with SMA were enrolled. Multiplex ligation-dependent probe amplifcation was used to measure the gene copy numbers of SMN1 and SMN2. The association of copy number of SMN1 and SMN2 with clinical phenotypes was analyzed. Results Of the 45 children with SMA, 42 (93%) had a homozygous deletion of SMN1 exons 7 and 8, and 3 (7%) had a deletion of SMN1 exon 7 alone. No association was found between SMA clinical types and the deletion types of SMN1 exons 7 and 8 (P > 0.05). There was a signifcant difference in the distribution of SMN2 gene copy numbers between the children with SMA and the healthy children (P < 0.05). The children with SMA usually had two or three copies of SMN2 gene, while the healthy children usually had one or two copies of SMN2 gene. There was a significant difference in the distribution of SMN2 copy numbers among the children with different SMA clinical types (P < 0.05). The children with two copies of SMN2 gene had a signifcantly lower age of onset than those with three or four copies. Most of the children with type I SMA had two or three copies of SMN2 gene. Most of the children with type Ⅱ SMA had three copies of SMN2 gene. Most of the children with type Ⅲ SMA had three or four copies of SMN2 gene. Children with a higher copy number of SMN2 gene tended to have an older age of onset and better motor function and clinical outcome, and there was a signifcant association between SMN2 gene copy number and clinical outcome (P < 0.05). Conclusions The SMN2 gene can reduce the severity of SMA via the dosage compensation effect. SMN2 copy number is associated with the phenotype of SMA, and therefore, it can be used to predict disease severity.