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Sarcoglycanopathies: an update
Neuromuscular Disorders ( IF 2.7 ) Pub Date : 2021-07-28 , DOI: 10.1016/j.nmd.2021.07.014
Mariz Vainzof 1 , Lucas S Souza 1 , Juliana Gurgel-Giannetti 2 , Mayana Zatz 1
Affiliation  

Sarcoglycanopathies are the most severe forms of autosomal recessive limb-girdle muscular dystrophies (LGMDs), constituting about 10–25% of LGMDs. The clinical phenotype is variable, but onset is usually in the first decade of life. Patients present muscle hypertrophy, elevated CK, variable muscle weaknesses, and progressive loss of ambulation. Four subtypes are known: LGMDR3, LGMDR4, LGMDR5 and LGMDR6, caused, respectively, by mutations in the SGCA, SGCB, SGCG and SGCD genes. Their four coded proteins, α-SG, ß-SG, λ-SG and δ-SG are part of the dystrophin-glycoprotein complex (DGC) present in muscle sarcolemma, which acts as a linker between the cytoskeleton of the muscle fiber and the extracellular matrix, providing mechanical support to the sarcolemma during myofiber contraction.

Many different mutations have already been identified in all the sarcoglycan genes, with a predominance of some mutations in different populations. The diagnosis is currently based on the molecular screening for these mutations. Therapeutic approaches include the strategy of gene replacement mediated by a vector derived from adeno-associated virus (AAV). Pre-clinical studies have shown detectable levels of SG proteins in the muscle, and some improvement in the phenotype, in animal models. Therapeutic trials in humans are ongoing.



中文翻译:

肌聚糖病:更新

肌聚糖病是常染色体隐性遗传性肢带型肌营养不良症 (LGMDs) 的最严重形式,约占 LGMDs 的 10-25%。临床表型是可变的,但通常在生命的头十年发病。患者出现肌肉肥大、CK 升高、不同程度的肌肉无力和进行性丧失行走能力。已知四种亚型:LGMDR3、LGMDR4、LGMDR5 和 LGMDR6,分别由SGCA、SGCB SGCGSGCD中的突变引起基因。它们的四种编码蛋白 α-SG、β-SG、λ-SG 和 δ-SG 是肌肉肌膜中存在的肌营养不良蛋白-糖蛋白复合物 (DGC) 的一部分,它充当肌纤维细胞骨架和肌纤维之间的连接体。细胞外基质,在肌纤维收缩期间为肌膜提供机械支撑。

已经在所有肌聚糖基因中鉴定出许多不同的突变,其中一些突变在不同人群中占优势。目前的诊断是基于对这些突变的分子筛查。治疗方法包括由腺相关病毒 (AAV) 衍生的载体介导的基因置换策略。临床前研究表明,在动物模型中,肌肉中的 SG 蛋白水平可检测,并且表型有所改善。人体治疗试验正在进行中。

更新日期:2021-07-28
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