X-连锁扩张型心肌病患者杜兴氏肌营养不良基因突变分析及临床评价

Mutation analysis of dystrophin gene and clinical evaluation of phenotypes in X-linked dilated cardiomyopathy.

目的 对X -连锁扩张型心肌病患者进行杜兴氏肌营养不良基因 (Dystrophin基因 )突变分析 ,并探讨基因型与表现型的关系。方法 从 10位X -连锁扩张型心肌病家系成员及 10 0位正常人外周血淋巴细胞中提取基因组DNA。应用PCR方法扩增先证者Dystrophin基因 5’端的肌肉亚型启动子、外显子 1～ 5及各剪切点并测序。应用限制性内切酶分析法分析所发现序列变化在家系中及正常人群中的分布情况。结果 序列分析检出一个位于第一外显子和内含子交界部的剪切点突变exon 1+1G >T。家系中基因型阳性的成员中 ,2位男性均患病 ,4位女性携带者中 1位患病 ,1位心脏彩超检查呈早期心肌病所见 ,基因型阴性成员均未患病。 10 0位正常人中无此突变。结论 Dystrophin基因剪切点突变exon 1+1G >T是导致X -连锁扩张型心肌病的致病性突变。对于X -连锁扩张型心肌病患者女性亲属也应确定其携带者状态 ,并对确认的携带者进行随访观察。

Objective To perform genetic mutation analysis and clinically evaluate the phenotypes in patients with X-linked dilated cardiomyopathy. Methods Genomic DNA was extracted from the peripheral lymphocytes of 10 family members from a X-linked recessive pedigree with dilated cardiomyopathy and 100 healthy controls.DNA fragments including dystrophin muscle promoter,exon 1-5 and splice junctions were amplified by PCR from the genomic DNA of the proband and were sequenced. Restriction analysis was used to analyze the distribution of the mutation among family members and healthy controls.Results A splice site mutation of dystrophin gene exon 1+1 G>T was identified.This mutation was present in two affected males and four female carriers and absent in unaffected family members and healthy controls.One of the four female carriers was affected and another had borderline echocardiograghy.Conclusion Splice site mutation exon 1+1 G>T is the etiologic mutation in this family.Screening of female carrier state and follow-up study of the confirmed carriers are important for X-liked DCM family.