Pathophysiological roles of DUX4 in FSHD1

DUX4 downstream signaling in FSHD. Low D4Z4 subunit methylation, which is caused either by low amount of D4Z4 subunits combined with a permissive 4q haplotype, or a mutation in genes involved with D4Z4 methylation, results in the expression of DUX4. Normally, DUX4 is only expressed during embryogenesis, after which it is silenced. Abnormal activation of DUX4 after silencing results in the muscle disease known as facioscapulohumeral muscular dystrophy, or FSHD.

在FSHD（面肩肱肌营养不良症）中，DUX4下游信号传导机制。D4Z4亚单位的低甲基化，可能由D4Z4亚单位数量减少并结合允许的4q等位基因型，或涉及D4Z4甲基化的基因突变所引起，导致DUX4的表达。通常，DUX4仅在胚胎发生期间表达，之后被沉默。沉默后的DUX4异常激活导致被称为面肩肱肌营养不良症的肌肉疾病。