Li Haoran, Yu Bo, Yuan Ye, Chen Nannan, Wu Jimeng, Zhang Zhiqing
Department of Pharmacy, The Second Hospital of Hebei Medical University, 215 Heping West Road, Shijiazhuang, 050000, Hebei Province, China.
Department of Pediatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, China.
Orphanet J Rare Dis. 2025 Jul 10;20(1):353. doi: 10.1186/s13023-025-03857-3.
Spinal Muscular Atrophy (SMA) is a neuromuscular disorder precipitated by mutations or deletions in the Survival Motor Neuron 1 (SMN1) gene. Although the SMN2 gene partially compensates for SMN1 functional deficiency, its expression is regulated by complex epigenetic and environmental factors. This review comprehensively elucidates the regulatory mechanisms through which epigenetic modifications-encompassing DNA methylation, histone modifications, and non-coding RNAs-modulate SMN2 gene expression and impact SMA pathogenesis and progression. We also briefly discuss how these epigenetic mechanisms may interact with selected environmental factors in modifying disease outcomes. Emerging evidence suggests that these epigenetic factors and environmental exposures interact synergistically to influence disease trajectory and may account for the heterogeneity observed in SMA clinical manifestations. These insights have given rise to novel therapeutic strategies, including pharmacological interventions targeting epigenetic pathways and optimized management of environmental factors. Integrating multi-omics analyses holds promise for advancing personalized precision medicine approaches for SMA and potentially improving patient outcomes.
脊髓性肌萎缩症（SMA）是一种神经肌肉疾病，由生存运动神经元1（SMN1）基因的突变或缺失引发。尽管SMN2基因可部分补偿SMN1的功能缺陷，但其表达受复杂的表观遗传和环境因素调控。本综述全面阐明了包括DNA甲基化、组蛋白修饰和非编码RNA在内的表观遗传修饰调节SMN2基因表达并影响SMA发病机制和进展的调控机制。我们还简要讨论了这些表观遗传机制如何与特定环境因素相互作用以改变疾病结局。新出现的证据表明，这些表观遗传因素和环境暴露相互协同作用，影响疾病发展轨迹，并可能解释SMA临床表现中观察到的异质性。这些见解催生了新的治疗策略，包括针对表观遗传途径的药物干预和对环境因素的优化管理。整合多组学分析有望推进SMA的个性化精准医疗方法，并可能改善患者预后。
