脊髓性肌萎缩症基因诊断  

Genetic diagnosis and gene sequencing of spinal muscular atrophy

作　　者：李文磊[1] 丁新生[1] 吴婷[1] 姚娟[1] 邓晓萱[1] 

机构地区：[1]南京医科大学第一附属医院神经内科,210029

出　　处：《中华神经科杂志》2005年第7期426-429,共4页Chinese Journal of Neurology

基　　金：江苏省教委自然科学基金资助项目(JW970091);江苏省科委应用基金资助项目(BJ980083);江苏省卫生厅重点资助项目(H2011)

摘　　要：目的探讨中国人儿童型脊髓性肌萎缩症(SMA)的基因序列、基因缺失情况及错配聚合酶链反应限制性片段长度多态性分析(PCRRFLP)技术在儿童型SMA基因诊断中的价值。方法应用错配PCRRFLP分析对34例拟诊为儿童型SMA(Ⅰ型18例,Ⅱ型11例,Ⅲ型5例)的患者、20名SMA患者的健康家系成员及20名健康人进行运动神经元存活基因(SMN)7号外显子缺失检测,并选择1例SMA患者的SMNc和1例健康人的SMNt基因7号外显子进行基因测序。结果34例拟诊SMA患者31例(91.2%)有SMNt7号外显子缺失,其中Ⅰ型18例,Ⅱ型10例,Ⅲ型3例,所有健康人均无SMN7号外显子缺失。SMNc和SMNt基因7号外显子测序长度均为187bp,两者的序列只有1个碱基的差异(T→C),与国外报道一致。结论中国人儿童型SMA基因序列与国外报道一致,Ⅰ～Ⅱ型基因缺失频率高,Ⅲ型缺失频率较低,错配PCRRFLP可作为诊断Ⅰ、Ⅱ型SMA的有效手段。Objective To study gene sequence and the frequency of gene deletion of childhoodonset spinal muscular atrophy （SMA） in China, and the value of the mismatching polymerase chain reactionrestriction fragment length polymorphism （PCR-RFLP） in gene diagnosis on SMA. Methods PCR-RFLP method was used to detect the homozygous deletion of the exon 7 of SMN gene in 34 presumed SMA patients（ 18 with type Ⅰ , 11 with type Ⅱ , 5 with type Ⅲ ） and 20 normal familial members of these patients and 20 normal individuals. Meanwhile, centromeric SMN gene of one SMA patient and telomeric SMN gene of one normal member were selected to perform gene sequencing. Results Homozygous deletion of exon 7 of the SMN gene was detected in 31 of 34 （91.2%） cases of presumed SMA, among which 18 in type Ⅰ ,10 in type Ⅱ , 3 in type Ⅲ, and no homozygous deletion was found in the normal controls; the sequence lengths of the exon 7 of telomeric and centromeric SMN gene were both 187 bp, and there was only one nucleotide difference between the two sequences （T→C）, which was identical to foreign reports. Conclusions The gene sequence of Chinese patients with childhood-onset SMA was coincident to foreigners, the percentage of homozygous deletion of the exon 7 of the SMN gene was high in type Ⅰ and Ⅱ SMA patients, yet the percentage was low in type Ⅲ SMA patients. Mismatching PCR-RFLP might be recommended as an effective diagnosis for type Ⅰ and Ⅱ SMA patients.

关 键 词：脊髓性肌萎缩症 基因诊断 运动神经元存活基因 碱基错配 聚合酶链反应 

分 类 号：R744[医药卫生—神经病学与精神病学]