Spinal Muscular Atrophy (SMA) is a neuromuscular disorder caused by mutations in the SMN1 gene. Being a monogenic disease, it is characterized by high clinical heterogeneity. Variations in penetrance and severity of symptoms, as well as clinical discrepancies between affected family members can result from modifier genes influence on disease manifestation. SMN2 gene copy number is known to be the main phenotype modifier and there is growing evidence of additional factors contributing to SMA severity. Potential modifiers of spinal muscular atrophy can be found among the wide variety of different factors, such as multiple proteins interacting with SMN or promoting motor neuron survival, epigenetic modifications, transcriptional or splicing factors influencing SMN2 expression. Study of these factors enables to reveal mechanisms underlying SMA pathology and can have pronounced clinical application.

中文翻译：

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参与脊髓性肌萎缩通路的分子因素作为可能的疾病修饰候选物

脊髓性肌萎缩症 (SMA) 是一种由 SMN1 基因突变引起的神经肌肉疾病。作为一种单基因疾病，它的特点是临床异质性高。外显率和症状严重程度的差异以及受影响家庭成员之间的临床差异可能是由于修饰基因对疾病表现的影响所致。已知 SMN2 基因拷贝数是主要的表型修饰符，并且越来越多的证据表明导致 SMA 严重性的其他因素。脊髓性肌萎缩症的潜在调节因子可以在各种不同的因素中找到，例如与 SMN 相互作用或促进运动神经元存活的多种蛋白质、表观遗传修饰、影响 SMN2 表达的转录或剪接因子。