假肥大型肌营养不良症的基因突变和产前诊断研究

Study on Duchenne muscular dystrophy gene mutation and prenatal Diagnosis

目的了解中国人群DMD基因外显子突变的特点和产前诊断情况。方法应用多重连接依赖性探针扩增技术（multiplexligation-dependentprobeamplification，MLPA）和变性高效液相色谱（denaturinghighperformanceliquidchromatography，DHPLC）技术对Duchenne型假肥大型肌营养不良症（Duchennemusculardystrophy，DMD）患者及胎儿进行DMD基因检测并对结果进行统计分析。结果在388例DMD患者中发现缺失、重复和点突变3种突变类型，其中缺失突变230例，占59．28％，重复突变43例，占11．08％。共发现2个缺失热点区域，分别涉及第45～54外显子和第3～19外显子。重复突变主要位于第2～43外显子之间。发现点突变115例，占29．64％。对其中6例进行检测共发现5例点突变。在53例产前诊断中，共发现33例男胎，其中18例为患病胎儿。患病家庭在已知同意的前提下自主选择了终止妊娠。结论中国人DMD基因的突变特点与国外报道一致。产前诊断可避免DMD患儿出生。

Objective To explore the characteristics of DNA mutations underlying Duchenne muscular dystrophy and provide prenatal diagnosis. Methods Multiplex ligation-dependent probe amplification （MLPA） and denaturing high performance liquid chromatography （DHPLC） were applied for analyzing DMD gene mutations in 388 unrelated Chinese patients and 53 fetuses. Results Respectively, 230 and 43 subjects were found to harbor a deletion （59.28%） or duplication （11.08%）. Two deletion hot spots were identified, which have located at exons 45 54 and exons 3-19. Duplications were mainly detected at exons 2- 43. Point mutations were identified in 29. 64~ of patients. Fifty-three fetuses were prenatal diagnosed, among which 18 were identified as patients. Conclusion Frequencies of DMD gene deletions and duplications in China are similar to global data. Prenatal diagnosis can help to reduce births of DMD patients.