症状性女性迪谢内肌营养不良基因携带者五例临床、病理和基因特点

Clinical, myopathological and genetic features in five female manifesting carriers of Duchenne muscular dystrophy

目的 分析5例症状性女性迪谢内肌营养不良（DMD）基因携带者临床、骨骼肌病理和基因突变特点.方法 5例女性患者的发病年龄为生后至54岁,其中1例有DMD家族史.2例表现为四肢近端无力,1例心肌病伴随肌痛,1例四肢无力伴随室间隔缺损,1例运动不耐受.5例患者血清肌酸激酶均升高（1 000～ 31 815 U/L）.4例患者行骨骼肌病理检查,5例患者均行多重连接探针扩增方法检测DMD基因突变,1例用荧光原位杂交技术分析染色体核型.结果 4例患者骨骼肌组织化学染色均呈肌营养不良样改变,1例抗肌萎缩蛋白完全丢失,3例灶性丢失.基因检测证实4例患者存在DMD外显子缺失突变,1例患者染色体存在t（x;5） （p21;p14）.结论 症状性女性DMD基因携带者的临床表现和骨骼肌抗肌萎缩蛋白表达下降程度更倾向于贝克肌营养不良,我国症状性女性DMD基因携带者也存在染色体易位.

Objective To analyze the clinical,myopathological and genetic features in 5 female manifesting carriers of Duchenne muscular dystrophy （DMD）.Methods The age of onset of these 5 patients were from birth to 54 years old,one of which had a family history of DMD.Two patients presented with proximal weakness,one with myalgia and dilated cardiomyopathy,one with limb weakness and ventricular septal defect,and one with exercise intolerance.Serum creatine kinase concentrations were between 1 000-31 815 U/L.Muscle biopsies were performed in 4 patients.Dystrophin gene mutation analyses were carried out in 5 patients by multiplex ligation-dependent probe amplification.Karyotype study was done in one patient who had no dystrophin gene mutation.Results Muscle biopsy revealed markedly decreased dystrophin expression in one patient and a mosaic pattern with some fibers lacking or partially expressing dystrophin in 3 patients.Four patients were identified carrying exonic deletions of dystrophin gene and one had t（x;5） （p21 ;p14）.Conclusions The clinical manifestations and myopathological changes are more compatible with Becker muscular dystrophy.Chromosome translocation can be detected in Chinese female manifesting carrier.