Heart, Lung and Vascular Institute, Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Department of Neurology and Rehabilitation Medicine, Neuromuscular Center, University of Cincinnati Gardner Neuroscience Institute, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Cells. 2021 Feb 8;10(2):349. doi: 10.3390/cells10020349.
Novel genetic variants exist in patients with hereditary neuromuscular disorders (NMD), including muscular dystrophy. These patients also develop cardiac manifestations. However, the association between these gene variants and cardiac abnormalities is understudied. To determine genetic modifiers and features of cardiac disease in NMD patients, we have reviewed electronic medical records of 651 patients referred to the Muscular Dystrophy Association Care Center at the University of Cincinnati and characterized the clinical phenotype of 14 patients correlating with their next-generation sequencing data. The data were retrieved from the electronic medical records of the 14 patients included in the current study and comprised neurologic and cardiac phenotype and genetic reports which included comparative genomic hybridization array and NGS. Novel associations were uncovered in the following eight patients diagnosed with Limb-girdle Muscular Dystrophy, Bethlem Myopathy, Necrotizing Myopathy, Charcot-Marie-Tooth Disease, Peripheral Polyneuropathy, and Valosin-containing Protein-related Myopathy. Mutations in COL6A1, COL6A3, SGCA, SYNE1, FKTN, PLEKHG5, ANO5, and SMCHD1 genes were the most common, and the associated cardiac features included bundle branch blocks, ventricular chamber dilation, septal thickening, and increased outflow track gradients. Our observations suggest that features of cardiac disease and modifying gene mutations in patients with NMD require further investigation to better characterize genotype-phenotype relationships.
遗传性神经肌肉疾病（NMD）患者存在新的遗传变异，包括肌营养不良症。这些患者也会出现心脏表现。然而，这些基因变异与心脏异常之间的关联尚未得到充分研究。为了确定 NMD 患者的遗传修饰因子和心脏疾病特征，我们回顾了在辛辛那提大学肌肉萎缩症协会护理中心就诊的 651 名患者的电子病历，并对 14 名患者的临床表型进行了特征描述，这些患者的临床表型与他们的下一代测序数据相关。数据是从当前研究中包含的 14 名患者的电子病历中检索出来的，包括神经和心脏表型以及遗传报告，其中包括比较基因组杂交阵列和 NGS。在以下 8 名被诊断为肢带型肌营养不良症、Bethlem 肌病、坏死性肌病、Charcot-Marie-Tooth 病、周围性多发性神经病和富含 Valosin 的蛋白相关肌病的患者中发现了新的关联。COL6A1、COL6A3、SGCA、SYNE1、FKTN、PLEKHG5、ANO5 和 SMCHD1 基因的突变最为常见，相关的心脏特征包括束支传导阻滞、心室腔扩张、室间隔增厚和流出道梯度增加。我们的观察结果表明，NMD 患者的心脏疾病特征和修饰基因突变需要进一步研究，以更好地描述基因型-表型关系。
