Quantitative analyses of SMN1 and SMN2 based on real-time LightCycler PCR:: Fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy
Quantitative analyses of SMN1 and SMN2 based on real-time LightCycler PCR:: Fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy
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DOI：
10.1086/338627
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发表时间：
2002-02-01
影响因子：
9.8
通讯作者：
Wirth, B
中科院分区：
文献类型：
--
作者：
Feldkötter, M;Schwarzer, V;Wirth, B
脊髓性肌萎缩症（SMA）是人类常见的常染色体隐性遗传病，由存活运动神经元基因1 （SMN1）的纯合缺失引起。SMN2是一种拷贝基因，影响SMA的严重程度，未来可能用于SMA患者的体细胞基因治疗。我们提出了一种新的，快速，高度可靠的定量测试，基于实时LightCycler PCR扩增SMN1或SMN2。在329名携带者和对照组中检测并验证了SMN1拷贝。特异性为100%，敏感性为96.2%。通过对375例I型、II型和III型SMA患者的SMN2拷贝数的定量分析，发现SMN2拷贝数与SMA类型以及生存时间之间存在显著相关性。因此，80%的I型SMA患者携带一个或两个SMN2拷贝，82%的II型SMA患者携带三个SMN2拷贝，而96%的III型SMA患者携带三个或四个SMN2拷贝。在113例I型SMA患者中，9例携带一个SMN2拷贝存活
Spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans, caused by homozygous absence of the survival motor neuron gene 1 (SMN1). SMN2, a copy gene, influences the severity of SMA and may be used in somatic gene therapy of patients with SMA in the future. We present a new, fast, and highly reliable quantitative test, based on real-time LightCycler PCR that amplifies either SMN1 or SMN2. The SMN1 copies were determined and validated in 329 carriers and controls. The specificity of the test is 100%, whereas the sensitivity is 96.2%. The quantitative analysis of SMN2 copies in 375 patients with type I, type II, or type III SMA showed a significant correlation between SMN2 copy number and type of SMA as well as duration of survival. Thus, 80% of patients with type I SMA carry one or two SMN2 copies, and 82% of patients with type II SMA carry three SMN2 copies, whereas 96% of patients with type III SMA carry three or four SMN2 copies. Among 113 patients with type I SMA, 9 with one SMN2 copy lived