摘要目的 探讨女性有症状DMD变异携带者(MCs)临床、病理、基因变异特点及发病机制.方法 选择河北医科大学第三医院神经肌病科自2010年至2014年收治的2例女性MCs,对其家系的临床、骨骼肌病理资料进行分析,同时检测DMD基因变异和X染色体失活情况.结果 (1)2例女性MCs均表现不同程度四肢近端肌无力、萎缩,家系中有类似DMD/BMD表现者.(2)2个家系先证者骨骼肌病理符合女性MCs病理表现,家系1先证者以及家系2先证者、Ⅱ-5、Ⅲ-7常规GRQ带染色体核型分析为正常女性核型.(3)基因测序结果显示,家系1先证者和Ⅱ-7均发现DMD基因外显子61杂合性缺失.家系2先证者、Ⅱ-5和Ⅲ-7均发现DMD基因外显子12-43杂合性缺失,家系2Ⅳ-4发现外显子12-43纯合性缺失.(4)X染色体失活分析结果显示,家系1先证者、家系2先证者和Ⅲ-7X染色体失活检测均不能区分父母的等位基因.结论 (1)女性MCs临床症状严重程度差异大,与骨骼肌活检病理表现相对应;(2)女性MCs下肢骨骼肌选择性受累与DMD相似,但不对称性更为显著;(3)2个家系均发现DMD基因外显子缺失,男性患者临床表型-基因变异符合阅读框学说,女性MCs不符合.

abstractsObjective To analyze the clinical and pathological genetic features of two Duchenne muscular dystrophy (DMD) manifesting carriers (MCs) and their families,and investigate the possible pathogenesis of female MCs.Methods The clinical and muscle pathological data of two female MCs,admitted to our hospital from 2010 to 2014,and their families,were collected,and DMD gene mutation and X chromosome inactivation were detected.Results (1) The two female MCs had proximal limb weakness;both two families had DMD/BMD-like patients.(2) The muscle biopsy pathological presentation was in accordance with female MCs pathological features,proband of two families and Ⅱ-5 and Ⅲ-7 of family 2 were normal female karyotype.(3) Proband and Ⅱ-7 of family 1 had loss of heterozygosity of DMD gene exon61;proband,Ⅱ-5 and Ⅲ-7 of family 2 had loss of heterozygosity of exon12-43,and Ⅳ-4 of family 2 had homozygous deletions of exon12-43.(4) X chromosome inactivation analysis of two probands and Ⅲ-7 of family 2 was uninformative.Conclusions (1) The clinical manifestations of female MCs are various;the clinical symptoms are corresponding with histochemical expression of skeletal muscle biopsy.(2) The selective muscle involvement of female MCs is similar with DMD,but rectus femoris is relatively preserved.(3) The two families have exon deletion of DMD gene;the relationship between clinical phenotype and gene mutation in male patients consists with the reading frame theory,but female don' t.