78例脊肌萎缩症患者SMN1基因突变分析  

Analysis of SMN1 gene mutations in 78 patients with spinal muscular atrophy

作　　者：利婧[1] 朱瑜龄[1] 詹益鑫 李亚勤[1] 陈孟龙[1] 王倞[1] 何若洁 张成[1] Li Jing Zhu Yuling Zhan Yixin Li Yaqin Chen Menglong Wang Liang He Ruojie Zhang Cheng(Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China KingMed Diagnostics, Guangzhou, Guangdong 510200, China)

机构地区：[1]中山大学附属第一医院神经科,广州510080 [2]金域医学检验中心,广州510200

出　　处：《中华医学遗传学杂志》2017年第5期658-661,共4页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金（81471280,81271401）;国家自然科学基金青年科学基金（81601087）;国家自然科学基金-广东省联合基金重点资助项目（U1032004）;广东省科学技术厅2014年度公益研究与能力建设专项资金资助项目（2014A020212130）;广东省广州市2015年产学研专项项目（1561000153）

摘　　要：目的分析脊肌萎缩症（spinal muscularatrophy，SMA）患者运动神经元存活基因（survial motor neuron1，SMN1突变情况，了解SMNl基因缺失在SMA患者各亚型的分布及其对诊断的意义。方法应用多重连接依赖式探针扩增法对78例SMA患者及其父母的SMN1进行突变检测。结果89．7％（70／78）的患者SMN1基因突变类型为第7、8外显子纯合缺失；3．8％（3／78）的患者为SMN1基因第7外显子纯合缺失、第8外显子杂合缺失；3．8％（3／78）的患者为SMN1基因第7外显子纯合缺失，未检测到第8外显子缺失；另有2．6％（2／78）的患者为SMN1基因第7、8外显子杂合缺失；对78例患者父母SMN1基因进行突变检测，发现77例患者父母均为相应基因突变携带者，符合SMA常染色体隐性遗传的特点。而1例SMN1基因第7、8外显子纯合缺失的SMA1型患者，母亲为SMN1第7和8外显子杂合缺失，父亲SMN1基因未检测到缺失和重复。结论SMA患者中SMN1基因纯合缺失达95％以上，使基因分析辅助临床诊断成为可能。在纯合缺失患者中，未见单独第8外显子的纯合缺失，提示分析SMN1基因第7外显子的纯合缺失更具有诊断意义。Objective To explore the significance of SMN1 gene mutations among patients with spinal muscular atrophy （SMA） and the value of multiplex ligation dependent probe amplification （MLPA） for its diagnosis. Methods Potential mutations of the SMN1 gene were detected among 78 SMA patients with a MLPA assay. Results Homozygous deletion of SMN1 exons 7 and 8 was detected in 70 （89.7 %） of all patients. Homozygous deletion of exons 7 and heterozygous deletion of exon 8 was detected in 3 patients （3.8%）. Homozygous deletion of SMN1 exons 7 alone was detected in 3 patients （3.8~/oo）. Heterozygous deletion of SMNI exons 7 and 8 was detected in 2 patients （2.6~/00）. For 77 of the patients, both parents were found to carry heterozygous deletion of the SMN1 gene, which was consistent with the recessive inheritance of SMA. One patient with SMA type I was found to be rather rare. The patient was found to carry homozygous deletion of SMN1 exons 7 and 8, for which her mother was heterozygous, while no mutation was found in her father. Conclusion Homozygous deletion of the SMN1 gene have been detected in more than 95% of SMA patients. No homozygous deletion of exon 8 has been found. Homozygous deletion of exon 7 is more significant in the pathogenesis of SMA.

关 键 词：脊肌萎缩症 SMN1基因 多重连接依赖式探针扩增法 

分 类 号：R440[医药卫生—诊断学] R746[医药卫生—临床医学]