摘要
目的:检测Duchenne/Becker型肌营养不良症(DMD/BMD)患者基因缺失及其表达产物———抗肌营养不良蛋白在肌细胞中的变化,探讨其与临床病情的关系。方法:应用9对引物多重PCR技术对42例DMD/BMD患者进行基因检测;并采用免疫荧光抗体染色技术对5例DMD,2例BMD肌细胞膜上抗肌营养不良蛋白的表达观察分析,以2例正常人的肌组织作为对照。结果:共发现21例外显子缺失,缺失片段长度各异,其中16例(76.2%)累及中央缺失热区,5例(23.8%)位于5′端缺失热区,尤以48号外显子缺失频率最高。5例DMD患者胞膜抗肌营养不良蛋白染色阴性,其中1例未检出基因缺失,但抗肌营养不良蛋白无表达。2例BMD患者染色弱阳性,可见间断斑片状荧光带。结论:DMD/BMD病情轻重可能与基因缺失的数量和片段大小不呈平行关系,而是与外显子的缺失类型有密切关系;基因的表达受个体差异的影响,呈高度的遗传异质性。抗肌营养不良蛋白缺乏或表达异常是造成DMD/BMD表型的病理基础,其临床后果不仅取决于缺失程度,还取决于缺失区域的功能意义。
Aim： To detect the deletion distribution of dystrophin gene and dystrophin changes in muscle cells of the patients with Duchenne/Becker muscular dystrophy（DMD/BMD）, furthermore to investigate the relationship between them and clinical symptoms. Methods： 42 patients with DMD/BMD were screened by 9 primers multiplex PCR. The patients from 5 DMD and 2 BMD were detected by immunofluorescence technique for analyzing dystrophin located in muscle cell membrane, compared with 2 normal males. Results： The deletion of one or more exons was found in 21 patients. 16 cases（76.2 % ） were detected in the central region and 5 patients（23.8% ） in the 5＇ extreme region, especially in exon 48（6 patients）. Negative result of staining was seen in 5 DMD patients. Of these, one case of DMD had no detectable levels of dystrophin, but no deletion of DMD gene. Dystrophin immunostaining from two P, MD patients consisted of a discontinuous staining pattern around most fibers. Conclusion： It might be possible that some correlation existed between the type of gene deletion and the degree of severity of the disease. The amount and size of exon deletion may not affect the symptoms. DMD/BMD are highly heterogeneous in clinical manifestation and in inheritance pattern. The pathologic foundation of DMD and BMD is the absence or abnormal expression of dystrophin. The consequence of that depends not only on the degree, but also on the function.
出处
《中国应用生理学杂志》
CAS
CSCD
北大核心
2005年第4期453-456,共4页
Chinese Journal of Applied Physiology
基金
河北省自然科学基金资助课题(397402)
