脊髓性肌萎缩临床表型与SMN2基因拷贝数变化的相关性研究

The study of the correlation between the clinical phenotype of spinal muscular atrophy and SMN2 gene copy number

目的探讨脊髓性肌萎缩（spinal muscular atrophy，SMA）的临床表型与运动神经元生存基因（survival motor neuron，SMN）拷贝数变化之间是否存在相关性。方法应用TaqMan技术的实时荧光定量PCR方法对57例不同临床表型的SMA患者的SMN2基因拷贝数进行检测。结果预测拷贝数为1的SM／Ve基因的平均拷贝数为1．017±0．090，变异系数（coefficient of variation，CV）值8．9％；预测拷贝数为2的SMN2基因的平均拷贝数为2．019±0．080，CV值3．9％；预测拷贝数为3的SMN2基因的平均拷贝数为3．104±0．170，CV值5．4％。Ⅰ型SMA患者SMNe基因平均拷贝数为1．926±0．460，Ⅱ型为2．508±0．460，Ⅲ型为2．876±0．270。Ⅱ型SMA患者SMN2平均拷贝数明显高于Ⅰ型（t=4．24，P〈0．01），Ⅲ型SMA患者SMN2平均拷贝数明显高于Ⅱ型（t=2．44，P〈0．01）。85．72％Ⅰ型SMA患者SMN2以2个拷贝为主；Ⅱ型SMA以2个和3个拷贝为主，分别占40％和60％；82％的Ⅲ型SMA则以3个拷贝为主。结论SMA临床表型的变化与SMN2基因拷贝数明显相关。不同类型SMA患者㈣拷贝数的分布不同：各型SMA患者至少有1个拷贝的Shine，11和Ⅲ型SMA患者的ShiNe拷贝数多于I型患者。提示疾病的严重程度依赖于SMN2拷贝数的变化。

Objective To detect the correlation between the chnical phenotype of spinal muscular atrophy （SMA） and survival motor neuron gene （ SMN2 ） copy number. Methods The SMN2 gene copy numbers of 57 different types of SMA were detected by real-time fluorescence quantitative PCR method with TaqMan technique. Results Average SMN2 copy number was 1. 017 ± 0. 090, 2. 019 ± 0. 080, 3. 104 ± 0. 170 in predicting one, two, three copy numbers, respectively, and CV was 8.9%, 3.9%, 5.4%, respectively. Average SMN2 copy number was 1.926±0. 460, 2.508±0.460, 2.876±0.270, in type Ⅰ , Ⅱ and Ⅲ SMA, respectively. TheSMN2 gene copy number in type Ⅱ and Ⅲ SMA were higher than that of type Ⅰ SMA （ P 〈 0.01）. The SMN2 gene copy number in type Ⅲ SMA was higher than that of type Ⅱ SMA（P 〈0.01）. 85.72% of type Ⅰ SMA patients usually had2SMN2 copies; 40% and 60% of type Ⅱ SMA patients had 2 and 3 SMW2 copies, respectively; 82% of type Ⅲ SMA patients had 3 SMW2 copies, Conclusion There is significant correlation between the change of SMA clinical phenotype and SMN2 cope number. The distributions of the SMN2 gene copy number are various in different types of SMA patients. All types of SMA patients have at least one copy SMN2 . The SMN2 gene copy numbers in type Ⅱ ,Ⅲ SMA are higher than that of type Ⅰ. All of these fmdings suggest that the severity of SMA patients depend on the change of the SMN2 copy numbers.