脊髓性肌萎缩症2个核心家系SMN1基因分析

Analysis of SMN1 gene in two Chinese families with spinal muscular atrophy

目的联合多重连接依赖探针扩增技术(multiplex ligation-dependent probe amplication,MLPA)和短串联重复序列(short tandem repeat,STR)基因连锁分析检测SMN1基因,分析父母及患者的遗传关系以提高携带者检出率。方法收集先证者及家系成员的资料,采用MLPA对先证者及其直系亲属SMN1基因的第7外显子及8外显子进行拷贝数检测,并对其家系进行STR分析。结果确诊的2例患儿均为SMN1基因第7和8外显子纯和缺失,母亲为携带者,父亲为"2+0"携带者,家系2胎儿为携带者。结论 MLPA能检测SMN基因外显子突变情况,STR连锁可分析风险染色体的来源,所以STR连锁分析能发现MLPA检测不到的携带情况。将两种方法结合可以减少对携带者的误判,为高危胎儿的受累风险提供准确遗传咨询。

Objective To identify survival motor neuron gene by application of multiplex ligation-dependent probe amplification(MLPA)and short tandem repeat(STR),analyze the genetic relationship between parents and the fetus to improve the detection rate of carriers.Methods Clinical features of two Chinese families were collected and MLPA was applied to detect the SMN1 gene for identifying the genetic copy of exon 7and 8.Short tandem repeat was analyzed at the same time.Results Both of probands had deletion of exons 7and 8,his mother had heterozygous deletions of exons7,and his father showed a'2+0'genotype,fetuse of the Family 2is carrier.Conclusion MLPA can detect mutation in the exons of SMN,while STR linkage analysis can provide the sources of risk chromosome,so it can detect the carriers in which no mutation are detected with MLPA.By combining the two methods,accurate information to high-risk fetus can be greatly improved of the genetic counseling.