Maretina Marianna A, Zheleznyakova Galina Y, Lanko Kristina M, Egorova Anna A, Baranov Vladislav S, Kiselev Anton V
D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Mendeleevskaya line, 3, Saint Petersburg199034, Russia.
Saint Petersburg State University, Universitetskaya emb. 7/9, 199034Saint Petersburg, Russia.
Curr Genomics. 2018 Aug;19(5):339-355. doi: 10.2174/1389202919666180101154916.
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.
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，它具有高度的临床异质性。修饰基因对疾病表现的影响可导致症状的外显率和严重程度的变化，以及受影响家庭成员之间的临床差异。已知SMN2基因拷贝数是主要的表型修饰因子，并且越来越多的证据表明还有其他因素导致SMA严重程度增加。在各种各样的不同因素中可以找到脊髓性肌萎缩症的潜在修饰因子，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。对这些因素的研究有助于揭示SMA病理的潜在机制，并可具有显著的临床应用价值。
