Zhang Yinhong, He Jing, Zhang Yunqian, Li Li, Tang Xinhua, Wang Lei, Guo Jingjing, Jin Chanchan, Tighe Sean, Zhang Yuan, Zhu Yingting, Zhu Baosheng
Department of Medical Genetics, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology.
Faculty of Life Science and Biotechnology, Kunming University of Science and Technology.
Medicine (Baltimore). 2020 Jan;99(3):e18809. doi: 10.1097/MD.0000000000018809.
In this article, the correlation between the copy number of survival motor neuron 2 (SMN2) gene, neuronal apoptosis inhibitory protein (NAIP), and the phenotype of spinal muscular atrophy patients were analyzed.Forty patients with spinal muscular atrophy (SMA) were included in the study at the Department of Medical Genetics of the First People's Hospital and the Department of Neurology of the Second People's Hospital in Yunnan Province from January 2012 to September 2018. Multiplex ligation-dependent probe amplification assay was performed to determine the copy numbers of SMN2 and NAIP genes. Statistical analysis was performed to determine the correlation between copy numbers of the SMN2 and NAIP genes and the clinical phenotypes of SMA.Our results show that among the 40 SMA patients, there were 13 type I cases, 16 type II cases and 11 type III cases. A total of 37 patients possessed a homozygous deletion of SMN1 exons 7 and 8, while the other 3 SMA patients possessed a single copy of SMN1 exon 8. There was no correlation between SMA subtypes and the deletion types of SMN1 exon 7 and 8 (P = .611). The percentage of 2, 3, and 4 copies of SMN2 exon 7 was 25.0%, 62.5%, and 12.5%, respectively. The percentage of 0, 1, and 2 copies of NAIP exon 5 was 10%, 57.5%, and 32.5%, respectively. The distributions of SMN2 and NAIP copy numbers among various SMA types were significantly different (all P < .05). Five combined SMN1-SMN2-NAIP genotypes were detected, of which 0-3-1 genotype had the highest proportion than the others, accounting for 42.5%. The copy number of SMN2 and NAIP gene had synergistic effect on SMA phenotype. The combined SMN1-SMN2-NAIP genotypes with fewer copies were associated with earlier onset age, higher mortality, and smaller average age at death in SMA patients.Therefore, we conclude that the copy number variance of SMN2 and NAIP is correlated with the SMA phenotype. Analysis of the copy number structure of the SMN1-SMN2-NAIP gene is helpful for SMA typing, disease prognosis prediction, and genetic counseling.
本文分析了生存运动神经元2（SMN2）基因、神经元凋亡抑制蛋白（NAIP）的拷贝数与脊髓性肌萎缩症患者表型之间的相关性。2012年1月至2018年9月，云南省第一人民医院医学遗传科和第二人民医院神经内科纳入了40例脊髓性肌萎缩症（SMA）患者进行研究。采用多重连接依赖探针扩增法检测SMN2和NAIP基因的拷贝数。进行统计分析以确定SMN2和NAIP基因拷贝数与SMA临床表型之间的相关性。我们的结果显示，40例SMA患者中，I型13例，II型16例，III型11例。共有37例患者存在SMN1外显子7和8的纯合缺失，另外3例SMA患者有1个SMN1外显子8拷贝。SMA亚型与SMN1外显子7和8的缺失类型之间无相关性（P = 0.611）。SMN2外显子7的2、3和4拷贝的百分比分别为25.0%、62.5%和12.5%。NAIP外显子5的0、1和2拷贝的百分比分别为10%、57.5%和32.5%。不同SMA类型中SMN2和NAIP拷贝数的分布有显著差异（均P < 0.05）。检测到5种SMN1-SMN2-NAIP联合基因型，其中0-3-1基因型比例最高，占42.5%。SMN2和NAIP基因拷贝数对SMA表型有协同作用。拷贝数较少的SMN1-SMN2-NAIP联合基因型与SMA患者发病年龄较早、死亡率较高及平均死亡年龄较小有关。因此，我们得出结论，SMN2和NAIP的拷贝数变异与SMA表型相关。分析SMN1-SMN2-NAIP基因的拷贝数结构有助于SMA分型、疾病预后预测及遗传咨询。
