一个常染色体显性遗传Emery-Dreifuss型肌营养不良家系的基因突变分析

Mutation analysis of a Chinese family with autosomal dominant Emery-Dreifuss muscular dystrophy

目的探讨一个常染色体显性遗传Emery-Dreifuss型肌营养不良（Emery-Dreifuss muscular dystrophy，EDMD）家系的临床、病理及遗传学特点。方法收集家系中2例患者（先证者及女儿）的临床资料及骨骼肌标本，行组织化学染色病理分析；收集先证者及家系成员（3代7人）血液DNA标本，采用聚合酶链反应和DNA直接测序方法对LMNA基因进行突变检测；明确基因变异位点后对家系行单倍型分析。结果先证者具有典型的EDMD临床表现：关节挛缩、进行性加重的肌无力和肌萎缩、心脏传导异常；骨骼肌活检病理示肌源性合并轻度神经源性改变；2例患者LMNA基因第9外显子发现杂合错义突变1583（C—G）（T528R），表型正常的其他家系成员未发现该突变；单倍型分析显示先证者及女儿具有相同的致病单倍型。结论报道了中国人常染色体显性遗传EDMD患者的表现型及基因型。

Objective To investigate the clinical, pathological and genetic characteristics in a family with autosomal dominant Emery-Dreifuss muscular dystrophy （AD-EDMD）. Methods Clinical data and skeletal muscle specimens were collected from two patients （the proband and her daughter） for pathological analysis. DNA samples of the prohand and her family members （7 persons from 3 generations） were obtained for PCR amplification and direct DNA sequencing of the lamin A/C （LMNA） gene. Haplotype analysis was performed after the identification of mutation. Results The proband had typical clinical maniSestation of EDMD： joint contracture, progressive muscle weakness and atrophy and cardiac conduction dysfunction. Muscular pathology revealed myopathic changes combined with slight neuropathic changes. A heterozygous missense mutation 1583 （C→G） （T528R） was identified in exon 9 of the LMNA gene in the two patients, but not in other family members. Haplotype analysis indicated that the proband and her daughter shared the same causative haplotype. Conclusion This is the first report of the phenotype and genotype of AD-EDMD in Chinese.