一个杜氏肌营养不良家系抗肌萎缩蛋白基因的突变检测

摘要

Objective To identify mutations of dystrophin gene in a Chinese pedigree affected with Duchenne muscular dystrophy (DMD).Methods Clinical data from the pedigree was collected.Subsequently,polymerase chain reaction and DNA sequencing analysis were applied to detect the potential mutations.Restriction enzyme digestion was carried out to determine whether the mutation was present in 118 healthy controls.Clustal software was applied for analyzing the conservation of altered amino acids.Results DNA sequencing analysis has identified a heterozygous missense mutation c.7578G ＞ C (p.Gln2526His) mutation in exon 52 of the dystrophin genein the proband and his mother.The same mutation was absent in the 118 healthy controls.Restriction enzyme digestion has confirmed above result.Clustal analysis indicated that the altered amino acid is highly conserved in mammals.Conclusion The results revealed a novel missense mutation (c.7578G＞C) of the dystrophin gene in DMD patients.%目的 研究1个杜氏肌营养不良家系抗肌萎缩蛋白基因(dystrophin基因)的突变情况.方法 收集杜氏肌营养不良患者及其家系的相关临床资料,应用聚合酶链反应及直接测序法对先证者及其家系成员进行dystrophin基因突变检测.针对发现的突变,在118名正常对照者中进行限制性内切酶分析,并用序列比对软件Clustal分析突变氨基酸的保守性.结果 测序结果显示先证者dystrophin基因第52外显子存在c.7578G＞C (p.Gln2526His)错义突变,先证者母亲的dystrophin基因第52外显子发生了c.7578G＞C错义杂合突变.而该突变不存在于118名正常对照者中,限制性内切酶法进一步证实了该结果.Clustal分析提示该突变氨基酸在哺乳动物进化上有高度的保守性.结论 该杜氏肌营养不良先证者的dystrophin基因上存在1个c.7578G＞C错义突变,该突变为一新的致病突变.