Rini Nicasio, Lupica Antonino, Alonge Paolo, Crescimanno Grazia, Pignolo Antonia, Messina Christian, Santa Paola Sandro, Giuliano Marika, Borgione Eugenia, Lo Giudice Mariangela, Scuderi Carmela, Di Stefano Vincenzo, Brighina Filippo
Department of Biomedicine, Neuroscience, and Advanced Diagnostic (BIND), University of Palermo, 90129 Palermo, Italy.
Oasi Research Institute-IRCCS, Via Conte Ruggero 73, 94018 Troina, Italy.
Genes (Basel). 2025 Aug 21;16(8):987. doi: 10.3390/genes16080987.
Limb-girdle muscular dystrophies (LGMDs) are a group of muscular dystrophies characterized by predominantly proximal-muscle weakness, with a highly heterogeneous genetic etiology. Despite recent efforts, the epidemiology of LGMDs is still under-evaluated. However, a better understanding of the distribution and genetic characteristics of LGMDs is required to optimize the diagnostic process and to address future research. Therefore, the aim of the present study is to investigate and identify new pathogenic variants, to better characterize LGMDs in Sicily. We enrolled patients with genetic and clinical diagnosis of LGMD referred to our clinic between the years 2019 and 2025. A targeted next-generation-sequencing (NGS) panel was performed, based on the reported disease frequency. A retrospective analysis of the clinical, laboratory, electrophysiological, and histological features was performed. A total of 28 LGMDs patients aged 56.6 years (47.2-60.5 IQR) were identified (16 males, 57%). A molecular diagnosis was achieved in 24 (85.7%) of patients, most commonly carrying mutations in (14 patients, 50%), followed by , , , and genes. Pathogenic variants in and were associated with earlier onset and longer disease duration, whereas presented later with a milder course. Cardiac involvement was observed more frequently in patients with and . Association between heterozygous mutations in the CAPN3 and DYSF, as well as between CAPN3 and DMD variants were reported. The findings of this study provide valuable insights into the epidemiology of LGMDs in the Western Sicily, offering important contributions to genotype-phenotype correlations. Our analysis highlights the role of genetic diagnosis in achieving accurate classification of the disease and optimizing clinical management.
肢带型肌营养不良症（LGMDs）是一组以近端肌肉无力为主的肌营养不良症，其遗传病因高度异质性。尽管最近有所努力，但LGMDs的流行病学仍未得到充分评估。然而，需要更好地了解LGMDs的分布和遗传特征，以优化诊断过程并开展未来研究。因此，本研究的目的是调查和鉴定新的致病变异，以更好地描述西西里岛LGMDs的特征。我们纳入了2019年至2025年间转诊至我们诊所的经基因和临床诊断为LGMDs的患者。基于报道的疾病频率进行了靶向二代测序（NGS）检测。对临床、实验室、电生理和组织学特征进行了回顾性分析。共鉴定出28例LGMDs患者，年龄56.6岁（四分位间距47.2 - 60.5）（16例男性，占57%）。24例（85.7%）患者获得了分子诊断，最常见的是携带（14例患者，占50%）的突变，其次是、、、和基因。和的致病变异与发病较早和病程较长有关，而发病较晚且病程较轻。在和的患者中更频繁地观察到心脏受累。报告了CAPN3和DYSF杂合突变之间以及CAPN3和DMD变异之间的关联。本研究结果为西西里岛西部LGMDs的流行病学提供了有价值的见解，为基因型 - 表型相关性做出了重要贡献。我们的分析强调了基因诊断在实现疾病准确分类和优化临床管理中的作用。
