儿童型脊肌萎缩症SMN基因缺失与微突变检测  

Detection of deletion and subtle mutations of SMN gene in children with spinal muscular atrophy

作　　者：杨晓苏[1] 邓益东[1] 肖波[1] 罗新明[1] 

机构地区：[1]中南大学湘雅医院神经内科,湖南长沙410008

出　　处：《中国当代儿科杂志》2005年第6期489-492,共4页Chinese Journal of Contemporary Pediatrics

基　　金：国家自然科学基金(No30170330);湖南省自然科学基金(02JJY3016)

摘　　要：目的研究儿童型脊肌萎缩症(SMA)患者中运动神经元生存基因缺失与微突变情况。方法收集经临床和肌肉活检确诊的SMA I^III型25例,其中I型5例,II型3例,III 17例及直系亲属24例。采用PCR-RFLP检测SMNt缺失情况,对无SMNt缺失的患者及SMA直系亲属,应用PCR-SSCP结合DNA序列分析的方法,进行SMN基因微突变分析。结果5例I型和3例II型SMA患者均见SMNt缺失,缺失率100%,6例III型见缺失,缺失率35%(6/17)。11例无缺失的SMA III型患者的gDNA编码区域未发现微突变;24例SMA的直系亲属中未发现SMN基因缺失及突变。结论①检测到SMNt外显子7缺失可作为SMA的确诊手段,有望替代肌电图和肌活检等有创检查;②对无SMNt外显子7缺失的III型SMA患者,要结合临床进行诊断;③该组无SMNt缺失的III型患者未发现微突变,提示存在遗传异质性。[中国当代儿科杂志,2005,7(6):489-492]Objective This study examined the prevalenee of deletion and subtle mutations of survival motor neuron （SMN） gene in ehihtren with spinal muscular atrophy （SMA）. Methods Polymerase chain reaetion-restriction fragment length polymorphlsm （PCR-RFLP） was used to detect the deletion of SMNt exon 7 in 25 children with SMA （ type Ⅰ 5 eases, type Ⅱ 3 eases, and type Ⅲ 17 cases ） and in 24 healthy relatives of these patients. SMA was diagnosed clinically and pathologically. The subtle mutations of SMN in encode regions were screened by polymerase chain reaetion-single strand eonformation polymorphism （ PCR-SSCP） combined with DNA direct sequencing in the patients without SMNt deletion and their relatives. Results Deletion of exon 7 of the SMNt gene was found in 5 eases of SMA type Ⅰ （ 100% ） , 3 eases of type Ⅱ （ 100% ） and 6, type＇ Ⅲ （ 35% ）. No subtle mutation of SMN was found in encoded regions in 11 cases of type Ⅲ SMA without SMNt deletion. The 24 relatives of SMA patients did not show the deletion and subtle mutation of SMN. Conclusions ①Deteetion of SMNt gene exon 7 deletion can he recommend as a definitive diagnostic method for SMA, and shuwed promise to replace invasive examinations, such as eleetrumyogram and muscular biopsy. ②In patients with type Ill SMA without SMNt deletion, diagnosis is still made clinically. ③No subtle mutation of SMN was found in SMA type Ⅲ patients without SMNt deletion, suggesting genetic heterogenicity might exist.

关 键 词：脊肌萎缩症 运动神经元生存基因 缺失 微突变 儿童 

分 类 号：R746[医药卫生—神经病学与精神病学]