Department of Neurology, Laboratory of Investigation in Neurology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Clinics (Sao Paulo). 2011;66(10):1713-9. doi: 10.1590/s1807-59322011001000008.
Limb-girdle muscular dystrophy presents with heterogeneous clinical and molecular features. The primary characteristic of this disorder is proximal muscular weakness with variable age of onset, speed of progression, and intensity of symptoms. Sarcoglycanopathies, which are a subgroup of the limb-girdle muscular dystrophies, are caused by mutations in sarcoglycan genes. Mutations in these genes cause secondary deficiencies in other proteins, due to the instability of the dystrophin-glycoprotein complex. Therefore, determining the etiology of a given sarcoglycanopathy requires costly and occasionally inaccessible molecular methods.
The aim of this study was to identify phenotypic differences among limb-girdle muscular dystrophy patients who were grouped according to the immunohistochemical phenotypes for the four sarcoglycans.
To identify phenotypic differences among patients with different types of sarcoglycanopathies, a questionnaire was used and the muscle strength and range of motion of nine joints in 45 patients recruited from the Department of Neurology--HC-FMUSP (Clinics Hospital of the Faculty of Medicine of the University of São Paulo) were evaluated. The findings obtained from these analyses were compared with the results of the immunohistochemical findings.
The patients were divided into the following groups based on the immunohistochemical findings: α-sarcoglycanopathies (16 patients), β-sarcoglycanopathies (1 patient), γ-sarcoglycanopathies (5 patients), and nonsarcoglycanopathies (23 patients). The muscle strength analysis revealed significant differences for both upper and lower limb muscles, particularly the shoulder and hip muscles, as expected. No pattern of joint contractures was found among the four groups analyzed, even within the same family. However, a high frequency of tiptoe gait was observed in patients with α-sarcoglycanopathies, while calf pseudo-hypertrophy was most common in patients with non-sarcoglycanopathies. The α-sarcoglycanopathy patients presented with more severe muscle weakness than did γ-sarcoglycanopathy patients.
The clinical differences observed in this study, which were associated with the immunohistochemical findings, may help to prioritize the mutational investigation of sarcoglycan genes.
肢带型肌营养不良症具有异质性的临床和分子特征。这种疾病的主要特征是近端肌肉无力，发病年龄、进展速度和症状严重程度各不相同。 sarcoglycanopathies 是肢带型肌营养不良症的一个亚组，由 sarcoglycan 基因突变引起。由于 dystrophin-glycoprotein 复合物的不稳定性，这些基因的突变会导致其他蛋白的继发性缺乏。因此，确定特定 sarcoglycanopathy 的病因需要昂贵且有时无法获得的分子方法。
本研究的目的是根据四种 sarcoglycan 的免疫组化表型对肢带型肌营养不良症患者进行分组，以确定表型差异。
为了确定不同类型 sarcoglycanopathy 患者之间的表型差异，我们使用问卷调查了来自神经内科--HC-FMUSP（圣保罗大学医学院附属医院）的 45 名患者，评估了 9 个关节的肌肉力量和运动范围。对这些分析的结果与免疫组化结果进行了比较。
根据免疫组化结果，患者分为以下几组：α-sarcoglycanopathies（16 例）、β-sarcoglycanopathies（1 例）、γ-sarcoglycanopathies（5 例）和非 sarcoglycanopathies（23 例）。肌肉力量分析显示，上肢和下肢肌肉，尤其是肩部和臀部肌肉，都有显著差异，这是意料之中的。在分析的四个组中，即使是在同一个家庭中，也没有发现关节挛缩的模式。然而，在患有α-sarcoglycanopathy 的患者中，高频率的踮脚步态，而在患有非 sarcoglycanopathy 的患者中，最常见的是小腿假性肥大。与γ-sarcoglycanopathy 患者相比，α-sarcoglycanopathy 患者的肌肉无力更为严重。
本研究中观察到的与免疫组化结果相关的临床差异，可能有助于优先进行 sarcoglycan 基因突变的调查。
