Comparison of X-chromosome inactivation in Duchenne muscle/myocardium-manifesting carriers, non-manifesting carriers and related daughters
Comparison of X-chromosome inactivation in Duchenne muscle/myocardium-manifesting carriers, non-manifesting carriers and related daughters
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DOI：
10.1111/cge.12048
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发表时间：
2013-09-01
影响因子：
3.5
通讯作者：
Politano, L.
中科院分区：
文献类型：
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作者：
Viggiano, E.;Picillo, E.;Politano, L.
杜氏肌营养不良症（DMD）的女性携带者通常没有症状。然而，他们中的2.5-7.8%可能会出现肌肉症状和心肌病，归因于肌营养不良蛋白的产生减少，可能是因为X染色体失活（XCI）的偏斜模式。为了评估XCI在有症状（在肌肉或心脏水平）和无症状DMD携带者中的作用，从我们的数据库中选择了44名受试者（12名表现，21名非表现，11名健康女性），并通过基于雄激素受体甲基化的测定在淋巴细胞中确定XCI模式。结果表明，DMD表现携带者具有携带正常等位基因的X染色体的优先失活，而非表现携带者和健康女性显示随机XCI模式。此外，当比较肌肉和心脏表现出载体时，前一组表现出更高程度的偏斜。当对有症状/无症状的母女对进行分析时，没有发现母亲和女儿之间XCI的一致性。结果证实携带者的DMD临床表现与X染色体失活的非随机模式有关。
Female carriers of Duchenne muscular dystrophy (DMD) are usually asymptomatic. However, 2.5-7.8% of them may present muscle symptoms and cardiomyopathy, attributed to a reduced production of dystrophin, probably because of skewed patterns of X-chromosome inactivation (XCI). To evaluate the role of XCI in symptomatic (at muscle or heart level) and asymptomatic DMD carriers, 44 subjects were selected from our database (12 manifesting, 21 non-manifesting, 11 healthy females), and XCI pattern determined in the lymphocytes by the androgen receptor methylation-based assay. The results showed that DMD-manifesting carriers had a preferential inactivation of the X-chromosome carrying the normal allele, while non-manifesting carriers and healthy females showed a random XCI pattern. Moreover, when comparing muscle with heart manifesting carriers, the former group showed a higher degree of skewing. No concordance in XCI was found between mothers and daughters, when symptomatic/asymptomatic mother-daughter pairs were analyzed. The results confirm that DMD clinical manifestations in carriers are associated with non-random patterns of X inactivation.