Sarcoglycanopathies comprise 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. In 2016, several clinicians involved in the diagnosis, management and care of patients with LGMDR3–6 created a European Sarcoglycanopathy Consortium. The aim of the present study was to determine the clinical and genetic spectrum of a large cohort of patients with sarcoglycanopathy in Europe. This was an observational retrospective study. A total of 33 neuromuscular centres from 13 different European countries collected data of the genetically confirmed patients with sarcoglycanopathy followed-up at their centres. Demographic, genetic and clinical data were collected for this study. Data from 439 patients from 13 different countries were collected. Forty-three patients were not included in the analysis because of insufficient clinical information available. A total of 159 patients had a confirmed diagnosis of LGMDR3, 73 of LGMDR4, 157 of LGMDR5 and seven of LGMDR6. Patients with LGMDR3 had a later onset and slower progression of the disease. Cardiac involvement was most frequent in LGMDR4. Sixty per cent of LGMDR3 patients carried one of the following mutations, either in a homozygous or heterozygous state: c.229C>T, c.739G>A or c.850C>T. Similarly, the most common mutations in LMGDR5 patients were c.525delT or c.848G>A. In LGMDR4 patients the most frequent mutation was c.341C>T. We identified onset of symptoms before 10 years of age and residual protein expression lower than 30% as independent risk factors for losing ambulation before 18 years of age, in LGMDR3, LGMDR4 and LGMDR5 patients. This study reports clinical, genetic and protein data of a large European cohort of patients with sarcoglycanopathy. Improving our knowledge about these extremely rare autosomal recessive forms of LGMD was helped by a collaborative effort of neuromuscular centres across Europe. Our study provides important data on the genotype-phenotype correlation that is relevant for the design of natural history studies and upcoming interventional trials in sarcoglycanopathies.

中文翻译：

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大型欧洲肌糖蛋白病患者队列中新的基因型-表型相关性。

肌糖蛋白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），分别由SGCA、SGCB、SGCG和SGCD突变引起基因。2016 年，几位参与 LGMDR3-6 患者诊断、管理和护理的临床医生创建了欧洲肌聚糖病联盟。本研究的目的是确定欧洲一大群肌糖蛋白病患者的临床和遗传谱。这是一项观察性回顾性研究。来自 13 个不同欧洲国家的总共 33 个神经肌肉中心收集了在其中心随访的经基因证实的肌糖蛋白病患者的数据。为这项研究收集了人口统计学、遗传和临床数据。收集了来自 13 个不同国家的 439 名患者的数据。由于可用的临床信息不足，43 名患者未纳入分析。共有 159 名患者确诊为 LGMDR3，73 名 LGMDR4，LGMDR5 的 157 个和 LGMDR6 的 7 个。LGMDR3 患者发病较晚，疾病进展较慢。心脏受累在 LGMDR4 中最为常见。60% 的 LGMDR3 患者携带以下突变之一，无论是纯合还是杂合状态：c.229C>T、c.739G>A 或 c.850C>T。同样，LMGDR5 患者中最常见的突变是 c.525delT 或 c.848G>A。在 LGMDR4 患者中，最常见的突变是 c.341C>T。我们将 LGMDR3、LGMDR4 和 LGMDR5 患者 10 岁前出现症状和残留蛋白表达低于 30% 确定为 18 岁前失去行走能力的独立危险因素。这项研究报告了欧洲一大群肌糖蛋白病患者的临床、遗传和蛋白质数据。通过欧洲神经肌肉中心的合作努力，提高了我们对这些极其罕见的常染色体隐性遗传形式的 LGMD 的认识。我们的研究提供了有关基因型-表型相关性的重要数据，这些数据与自然史研究的设计和即将进行的肌糖蛋白病干预试验相关。