脊肌萎缩症家系运动神经元生存基因微小突变的鉴定  

Subtle mutation analysis of survival motor neuron gene in families with spinal muscular atrophy

作　　者：曾健[1] 林炎鸿[1] 严爱贞[1] 兰风华[1] 

机构地区：[1]南京军区福州总医院遗传病分子诊断中心,350025

出　　处：《中华检验医学杂志》2012年第7期607-611,共5页Chinese Journal of Laboratory Medicine

摘　　要：目的建立一套运动神经元生存（SMN）基因微小突变检测体系，以评价其用于脊肌萎缩症（SMA）家系的价值。方法采用RNA水平和基因组DNA水平双途径检测策略，用PCR一限制性片段长度多态性（RFLP）、位点特异性PCR、多重连接依赖性探针扩增（MLPA）和T克隆测序技术对2个SMA家系共7个成员行SMN基因微小突变分析。结果用MLPA和T克隆测序技术检测家系A的SMA患者有1个拷贝的SMN1基因，其第228位密码子上存在1个无义突变L228X，该突变来源于患者父亲；家系B的SMA患者父亲有2个SMN1基因，其中1个SMN1基因存在移码突变22_23insA。其余家系成员均为有1个SMN1基因拷贝的SMA携带者。结论建立的SMN微小突变检测体系成功鉴定了2个SMN微小突变，为SMA家系的遗传咨询提供了可靠依据。Objective To establish a analytical system for the survival motor neuron （SMN） subtle mutation, and evaluate its application in two families with spinal muscular atrophy （SMA）. Methods SMN genes in seven family members from two SMA families were analyzed at both transcript level and genomic level, by the use of the conventional PCR-RFLP, allele-specific PCR, multiplex ligation-dependent probe amplification （MLPA） and T subcloning and sequencing of SMN1 gene. Results In family A, the patient had a single SMN1 copy who was carrying nonsense mutation L228X,which was also found in his father. In family B, as the patient＇s sample was unavailable, the father was indeed a carrier with one normal SMN1 allele and the other SMN1 allele carrying a frameshift mutation 22_23insA. The remaining family members were SMA carriers with one. SMN1 copy. Conclusion This analytical system for SMN subtle mutation offers viable molecular basis for genetic counseling and prenatal diagnosis in SMA families. （ Chin J Lab Med, 2012,35：607-611 ）

关 键 词：肌萎缩 脊髓性 系谱 运动神经元 运动神经元生存蛋白质1 突变 核 酸扩增技术 

分 类 号：R746[医药卫生—神经病学与精神病学]