Sarcoglycanopathies include four subtypes of autosomal recessive limb-girdle muscular dystrophies (LGMDR3, LGMDR4, LGMDR5 and LGMDR6) that are caused, respectively, by mutations in the SGCA, SGCB, SGCG and SGCD genes. Delta-sarcoglycanopathy (LGMDR6) is the least frequent and is considered an ultra-rare disease. Our aim was to characterize the clinical and genetic spectrum of a large international cohort of LGMDR6 patients and to investigate whether or not genetic or protein expression data could predict diseasés severity. This is a retrospective study collecting demographic, genetic, clinical and histological data of patients with genetically confirmed LGMDR6 including protein expression data from muscle biopsies. We contacted 128 pediatric and adult neuromuscular units around the world that reviewed genetic data of patients with a clinical diagnosis of a neuromuscular disorder. We identified 30 patients with a confirmed diagnosis of LGMDR6 of which 23 patients were included in this study. Eighty seven percent of the patients had consanguineous parents. Ninety one percent of the patients were symptomatic at the time of the analysis. Proximal muscle weakness of the upper and lower limbs was the most common presenting symptom. Distal muscle weakness was observed early over the course of the disease in 56.5% of the patients. Cardiac involvement was reported in 5 patients (21.7%) and 4 patients (17.4%) required non-invasive ventilation. Sixty percent of patients were wheelchair-bound since early teens (median age of 12.0 years old). Patients with absent expression of the sarcoglycan complex on muscle biopsy had a significant earlier onset of symptoms and an earlier age of loss of ambulation compared to patients with residual protein expression. This study confirmed that delta-sarcoglycanopathy is an ultra-rare neuromuscular condition and described the clinical and molecular characteristics of the largest yet-reported collected cohort of patients. Our results showed that this is a very severe and quickly progressive disease characterized by generalized muscle weakness affecting predominantly proximal and distal muscles of the limbs. Similar to other forms of sarcoglycanopathies, the severity and rate of progressive weakness correlates inversely with the abundance of protein on muscle biopsy.

中文翻译：

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一大群 δ-肌聚糖肌营养不良症患者的临床和遗传谱

肌聚糖病包括常染色体隐性遗传性肢带型肌营养不良症的四种亚型（LGMDR3、LGMDR4、LGMDR5 和 LGMDR6），它们分别由 SGCA、SGCB、SGCG 和 SGCD 基因的突变引起。Delta-sarcoglycanopathy (LGMDR6) 是最不常见的疾病，被认为是一种极为罕见的疾病。我们的目的是描述大型国际 LGMDR6 患者队列的临床和遗传谱，并研究遗传或蛋白质表达数据是否可以预测疾病的严重程度。这是一项回顾性研究，收集经基因证实的 LGMDR6 患者的人口统计学、遗传、临床和组织学数据，包括肌肉活检的蛋白质表达数据。我们联系了全球 128 个儿科和成人神经肌肉单位，这些单位审查了临床诊断为神经肌肉疾病的患者的基因数据。我们确定了 30 名确诊为 LGMDR6 的患者，其中 23 名患者被纳入本研究。87% 的患者有近亲。91% 的患者在分析时有症状。上肢和下肢近端肌肉无力是最常见的表现症状。56.5% 的患者在病程早期观察到远端肌肉无力。5 名患者（21.7%）报告心脏受累，4 名患者（17.4%）需要无创通气。60% 的患者从十几岁开始就坐轮椅（中位年龄为 12.0 岁）。与残留蛋白表达的患者相比，肌肉活检中肌糖聚糖复合物表达缺失的患者症状出现明显更早，且不能行走的年龄也更早。该研究证实 delta-sarcoglycanopathy 是一种极其罕见的神经肌肉疾病，并描述了迄今为止最大的一组患者的临床和分子特征。我们的研究结果表明，这是一种非常严重且进展迅速的疾病，其特征是全身肌肉无力，主要影响四肢的近端和远端肌肉。与其他形式的肌糖蛋白病类似，进行性虚弱的严重程度和发生率与肌肉活检中蛋白质的丰度成反比。