BACKGROUND Limb-girdle muscular dystrophy (LGMD) is a group of neuromuscular disorders of heterogeneous genetic etiology with more than 30 directly related genes. LGMD is characterized by progressive muscle weakness involving the shoulder and pelvic girdles. An important differential diagnosis among patients presenting with proximal muscle weakness (PMW) is late-onset Pompe disease (LOPD), a rare neuromuscular glycogen storage disorder, which often presents with early respiratory insufficiency in addition to PMW. Patients with PMW, with or without respiratory symptoms, were included in this study of Latin American patients to evaluate the profile of variants for the included genes related to LGMD recessive (R) and LOPD and the frequency of variants in each gene among this patient population. RESULTS Over 20 institutions across Latin America (Brazil, Argentina, Peru, Ecuador, Mexico, and Chile) enrolled 2103 individuals during 2016 and 2017. Nine autosomal recessive LGMDs and Pompe disease were investigated in a 10-gene panel (ANO5, CAPN3, DYSF, FKRP, GAA, SGCA, SGCB, SGCD, SGCG, TCAP) based on reported disease frequency in Latin America. Sequencing was performed with Illumina's NextSeq500 and variants were classified according to ACMG guidelines; pathogenic and likely pathogenic were treated as one category (P) and variants of unknown significance (VUS) are described. Genetic variants were identified in 55.8% of patients, with 16% receiving a definitive molecular diagnosis; 39.8% had VUS. Nine patients were identified with Pompe disease. CONCLUSIONS The results demonstrate the effectiveness of this targeted genetic panel and the importance of including Pompe disease in the differential diagnosis for patients presenting with PMW.

中文翻译：

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拉丁美洲在下一代测序遗传学小组中的经验，该遗传学小组针对隐性肢带肌肉无力和庞贝病。

背景技术腰带型肌营养不良症（LGMD）是一组具有30多个直接相关基因的异质遗传病因的神经肌肉疾病。LGMD的特征是进行性肌肉无力，涉及肩部和骨盆带。在表现为近端肌无力（PMW）的患者中，一项重要的鉴别诊断是晚期发作的庞贝病（LOPD），这是一种罕见的神经肌肉糖原贮积病，除PMW之外，还常常表现为早期呼吸功能不全。这项拉丁美洲患者的研究纳入了有或无呼吸系统症状的PMW患者，以评估与LGMD隐性（R）和LOPD相关的所含基因的变体概况，以及该患者人群中每个基因的变体频率。结果2016年和2017年，拉丁美洲（巴西，阿根廷，秘鲁，厄瓜多尔，墨西哥和智利）的20多家研究机构招募了2103名个体。在10个基因组（ANO5，CAPN3，DYSF）中调查了9种常染色体隐性LGMD和Pompe病，FKRP，GAA，SGCA，SGCB，SGCD，SGCG，TCAP）为基础，根据拉丁美洲报告的疾病频率。用Illumina的NextSeq500进行测序，并根据ACMG指南对变体进行分类。病原体和可能的病原体被视为一类（P），并描述了未知意义的变体（VUS）。在55.8％的患者中发现了遗传变异，其中16％的患者接受了明确的分子诊断。39.8％的患者有VUS。确定9名患者患有庞贝病。