女性Duchenne/Becker型肌营养不良症携带者发病机理的研究进展

Duchenne/Becker型肌营养不良(DMD/BMD)是一类常见的X连锁隐性遗传病,多见于男性患者,女性携带者一般不发病,因为女性体内会发生随机的X染色体失活,而使体内呈现镶嵌型。目前,越来越多的文献报道DMD/BMD女性携带者发病的病例,其症状有轻有重,但发病机制尚不明了,大多数研究认为与X染色体的偏斜失活有关,即携带DMD突变的X染色体异常活化,使正常DMD基因弱或无表达,从而无法生成正常功能的dystrophin蛋白,表现为DMD/BMD。本文主要综述了X偏斜失活与DMD女性携带者发病相关性的研究进展。

Advances in the Pathogenic Research of Female Carriers with Symptomatic Duchenne Muscular Dystrophy

ABSTRACT: DMD/BMD is a X-linked recessive hereditary disease. It predominantly affects males. While female carriers do not have symptoms, due to their inactive X chromosome make it present mosaic. Recently, more and more papers reported that a clinically significant proportion of DMD/BMD female carriers have symptoms. They presented variable degrees of symptoms. But the mechanism of the pathogencity is still not clear. Most of the research considered that the dominating reason is the skewed X inactivation. It means that the predominant expression of the DMD mutant allele make the normal one have weak expression, thus no function dystrophin pro- teins could be generate, manifested as DMD/BMD. In this paper, we mainly summarized the relationship between skewed X inactivation and pathogenicity of the symptomatic DMD female carriers.