强直性肌营养不良的分子诊断技术的临床应用研究

Clinical application of the molecular diagnostic technology for myotonic dystrophy

目的探讨强直性肌营养不良(MD)早期分子诊断方法的准确性、有效性、适用性.方法以150名正常人及8个家系共82名MD患者及成员为研究对象,应用长模板TM-PCR扩增法对其组织中MTPK基因3'端三核苷酸CTG重复拷贝数进行检测.结果150名正常人MTPK基因3'端三核苷酸CTG重复拷贝数均在5～37次之间,其中以13次频率为最多(83/150);8个家系82名受检者中86.5%(46/52)临床诊断患者与8名临床可疑患者CTG重复拷贝数高于正常;半数无症状者CTG重复拷贝数高于正常,并在后来随访中陆续出现症状;1例临床可疑MD女性患者个体的组织及其流产胎儿组织CTG重复拷贝数明显高于正常.结论运用长模板PCR扩增TM法来检测受检者DNA的分子诊断技术其准确性与有效性高,适用性广,对于MD的早期诊断及预测,对于优生优育、降低DM发病率具有重要价值,临床值得推广.

Objective To study the accuracy, efficacy and applicability of early molecular diagnostic technology in the diagnosis of myotonic dystrophy (MD). Methods With the help of Long Expand TM Template PCR system, we detected CTG trinucleotide repeat numbers located in the 3' untranslated region of the protein kinase gene (MTPK) of 150 normal persons and 82 MD patients coming from 8 MD pedigrees as objects. Results The CTG trinucleotide repeat numbers located in the 3' untranslated region of the protein kinase gene of 150 normal persons ranged from 5 to 37, in which the highest frequency was 13 (83/150). The CTG trinucleotide repeat numbers of 86.5% (46/52) of the MD patients diagnosed clinically and 8 susceptible individuals in clinic coming from 8 MD pedigrees were above the normal, so were half of the asymptomatic individuals' CTG trinucleotide repeat numbers in those pedigrees who successively appeared to have MD symptoms in our visits afterward. The CTG trinucleotide repeat numbers of a female susceptible individual in clinic and her abortus' tissue were also above the normal remarkably. Conclusion The molecular diagnostic technology used for checking the susceptible individuals' DNA by the Long Expand TM Template PCR system is of satisfactory accuracy, high validity and wide applicability. It deserves clinical popularization owing to its important significance in the early diagnosis, prediction of MD, prepotency and reduction of MD incidence.