Zhang Yin-Hong, Zhang Yun-Qian, Zhu Bao-Sheng, He Jing, Wang Lei, Tang Xin-Hua, Guo Jing-Jing, Jin Chan-Chan, Chen Hong, Zhang Jie, Zhang Jin-Man, Li Li
Genetic Diagnosis Center, Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, China.
Zhongguo Dang Dai Er Ke Za Zhi. 2019 Mar;21(3):239-243. doi: 10.7499/j.issn.1008-8830.2019.03.010.
To study the association of copy number of SMN1 and SMN2 with clinical phenotypes in children with spinal muscular atrophy (SMA).
A total of 45 children with SMA were enrolled. Multiplex ligation-dependent probe amplification 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.
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 significant 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 significantly 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 significant association between SMN2 gene copy number and clinical outcome (P<0.05).
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.
研究脊髓性肌萎缩症（SMA）患儿中SMN1和SMN2基因拷贝数与临床表型的相关性。
共纳入45例SMA患儿。采用多重连接依赖探针扩增技术检测SMN1和SMN2基因的拷贝数。分析SMN1和SMN2基因拷贝数与临床表型的相关性。
45例SMA患儿中，42例（93%）存在SMN1基因第7和8外显子的纯合缺失，3例（7%）仅存在SMN1基因第7外显子缺失。未发现SMA临床类型与SMN1基因第7和8外显子缺失类型之间存在关联（P>0.05）。SMA患儿与健康儿童之间SMN2基因拷贝数分布存在显著差异（P<0.05）。SMA患儿通常有2或3个SMN2基因拷贝，而健康儿童通常有1或2个SMN2基因拷贝。不同SMA临床类型患儿的SMN2拷贝数分布存在显著差异（P<0.05）。有2个SMN2基因拷贝的患儿发病年龄显著低于有3或4个拷贝的患儿。大多数I型SMA患儿有2或3个SMN2基因拷贝。大多数II型SMA患儿有3个SMN2基因拷贝。大多数III型SMA患儿有3或4个SMN2基因拷贝。SMN2基因拷贝数较高的患儿发病年龄往往较大，运动功能和临床结局较好，且SMN2基因拷贝数与临床结局之间存在显著关联（P<0.05）。
SMN2基因可通过剂量补偿效应减轻SMA的严重程度。SMN2拷贝数与SMA的表型相关，因此可用于预测疾病严重程度。
