The sarcoglycan complex in the six autosomal recessive limb-girdle muscular dystrophies
The sarcoglycan complex in the six autosomal recessive limb-girdle muscular dystrophies
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DOI：
10.1093/hmg/5.12.1963
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发表时间：
1996-12-01
影响因子：
3.5
通讯作者：
Zatz, M
中科院分区：
文献类型：
--
作者：
Vainzof, M;PassosBueno, MR;Zatz, M
为了加深对常染色体隐性肢带型肌营养不良症(LGMD)的认识，对6种不同遗传类型(LGMD2A~LGMD2F)的患者进行了针对4种肌糖亚基(α-、β-、γ-、β-SG)、抗肌营养不良蛋白(Dstrophin)、β-DG(β-DG)和麦球蛋白的抗体检测，LGMD2A和2B患者均有轻微的临床病程，而原发肌糖蛋白突变(LGMD2C~2F)的患者具有不同的临床严重程度，所有6例AR LGMD患者的肌营养不良蛋白和肌球蛋白免疫荧光图谱均为阳性。大多数具有严重Duchenne样表型的患者完全缺乏SG复合体，然而，在13q连锁的患者中发现了一些例外，这表明对于较轻的表型，SG成分的某些标记的存在可能不是预后。观察到主要缺乏α-SG导致完全缺乏β-和β-SG，而不是伽马-SG，这表明肌糖蛋白的α、β和三角洲亚基可能有更密切的联系，在原发肌糖蛋白突变的患者中可以看到肌营养不良蛋白的数量继发减少，这在原发β-糖蛋白突变患者中最为明显。相反，所有患者都保留了β-DG染色，这表明SG和DG亚复合体之间的联系并不那么强。基于上述发现，我们改进了DGC中已知的肌聚糖复合体糖蛋白之间的相互作用模型。
To enhance our understanding of the autosomal recessive limb-girdle muscular dystrophy (LGMD), patients from six genetically distinct forms (LGMD2A to LGMD2F) were studied with antibodies directed against four sarcoglycan subunits (alpha-, beta-, gamma-, delta-SG), dystrophin, beta-dystroglycan (beta-DG) and merosin, All patients with LGMD2A and 2B had a mild clinical course while those with a primary sarcoglycan mutation (LGMD2C to 2F) had a range of clinical severity, Dystrophin and merosin immunofluorescence pattern was positive in patients with all six AR LGMDs. The majority of patients with a severe Duchenne-like phenotype presented total absence of the SG complex, However, some exceptions were found in 13q linked patients, indicating that the presence of a certain labelling for components of the SG may not be prognostic for a milder phenotype, The observation that the primary absence of alpha-SG results in the total absence of beta- and delta-SG but not of gamma-SG suggests that the alpha-, beta- and delta-subunits of sarcoglycan may be more closely associated, A secondary reduction in dystrophin amount was seen in patients with primary sarcoglycan mutations, which was most marked in patients with primary beta-, gamma- and delta-SG deficiencies, In contrast, beta-DG staining was retained in all patients, suggesting that the association between SG and DG subcomplexes is not so strong. Based on the above findings, we have refined the model for the interaction among the known glycoproteins of the sarcoglycan complex, within the DGC.