Zeng Guangqun, Zheng Hong, Cheng Jing, Chen Rong, Lin He, Yang Jiyun, Zhang Dingding
Zunyi Medical University, Zunyi, Guizhou 563000, P. R. China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2014 Apr;31(2):152-5. doi: 10.3760/cma.j.issn.1003-9406.2014.02.006.
To assess the association of copy number variations of SMN1, SMN2, NAIP, GTF2H2 and H4F5 genes with clinical classification of spinal muscular atrophy in children, and determine the copy number of the SMN gene among pregnant women. A carrier screening was also performed in Sichuan province.
The copy number variations of the above genes among 53 confirmed SMA patients were determined with MLPA technique. The copy number variations were analyzed by the Fisher's exact test. Deletion of exon 7 in the SMN1 gene was screened with denaturing high performance liquid chromatography (DHPLC) for 427 pregnant women.
Among the 53 cases of type I, II, and III SMA patients, the rate of homozygous deletion of both exons 7 and 8 of the SMN1 gene were 100%, 94.44% and 87.50%, respectively, whereas those of homozygous deletion of exon 7 of SMN1 gene were 0, 5.56%, and 12.50%, respectively. The patients with 1, 2, 3, and 4 copies of exon 7 of the SMN2 gene were 11.32%, 67.92%, 13.21% and 7.55%, respectively. The patients with 0, 1, and 2 copies of exon 5 of NAIP gene were 11.32%, 62.26%, and 26.42%, respectively. No deletion was detected in GTF2H2 or H4F5 genes. The heterozygous loss rate of exon 7 in SMN gene in the pregnant women population of Sichuan region was approximately 2.11%.
Copy number variations of SMN2 and NAIP genes in patients are related to SMA clinical types (P < 0.05). In contrast, there was no relationship between SMA clinical types and deletion of exons 7 and 8 in the SMN1 gene (P > 0.05). Analysis of copy number change in SMN1 gene can assist SMA carrier screening. However, when the general population without SMA family history is screened for disease-causing genes, it should be noted that the type "2+0" carriers may affect the screening result, and the result should be interpreted with caution.
评估运动神经元存活基因1（SMN1）、运动神经元存活基因2（SMN2）、神经元凋亡抑制蛋白（NAIP）、通用转录因子ⅡH多肽2（GTF2H2）和组蛋白H4家族成员5（H4F5）基因拷贝数变异与儿童脊髓性肌萎缩症临床分型的相关性，并确定孕妇中SMN基因的拷贝数。同时在四川省进行携带者筛查。
采用多重连接探针扩增（MLPA）技术检测53例确诊的脊髓性肌萎缩症患者上述基因的拷贝数变异。采用Fisher精确检验分析拷贝数变异情况。应用变性高效液相色谱（DHPLC）技术对427例孕妇进行SMN1基因第7外显子缺失筛查。
在53例Ⅰ型、Ⅱ型和Ⅲ型脊髓性肌萎缩症患者中，SMN1基因第7和8外显子纯合缺失率分别为100%、94.44%和87.50%，而SMN1基因第7外显子纯合缺失率分别为0、5.56%和12.50%。SMN2基因第7外显子拷贝数为1、2、3和4的患者分别占11.32%、67.92%、13.21%和7.55%。NAIP基因第5外显子拷贝数为0、1和2的患者分别占11.32%、62.26%和26.42%。未检测到GTF2H2或H4F5基因缺失。四川地区孕妇群体中SMN基因第7外显子杂合缺失率约为2.11%。
患者中SMN2和NAIP基因的拷贝数变异与脊髓性肌萎缩症临床类型相关（P<0.05）。相反，脊髓性肌萎缩症临床类型与SMN1基因第7和8外显子缺失无关（P>0.05）。分析SMN1基因拷贝数变化有助于脊髓性肌萎缩症携带者筛查。然而，在对无脊髓性肌萎缩症家族史的普通人群进行致病基因筛查时，应注意“2+0”型携带者可能影响筛查结果，对结果的解读应谨慎。
