Wang Huaigen, Zhao Ronghui, Wang Jiaojiao, Han Xiu, Li Kaifeng, Gao Yafeng, Wang Ya, Ma Aiqun, Wang Tingzhong, Du Yuan
Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Department of Anaesthesiology and Surgery, The First Affiliated Hospital of Xian Jiaotong University, Xi'an, Shaanxi, China.
Medicine (Baltimore). 2024 Dec 13;103(50):e40875. doi: 10.1097/MD.0000000000040875.
Dilated cardiomyopathy (DCM) is characterized by ventricular dilation and poor systolic function. Approximately half of idiopathic DCM cases are assigned to genetic causes in familial or apparently sporadic cases, and more than 50 genes are reported to cause DCM. However, genetic basis of most DCM patients still keeps unknown and require further study. Clinical data, family histories, and blood samples were collected from the proband and family members in a Chinese family presenting with DCM and conduction system disease. A genetic analysis was performed using next generation sequencing (NGS). Bioinformatic analysis was performed to predict the pathogenic consequence of gene mutation. A missense heterozygous mutation c.652G > A (p.G218R) in Laminin Subunit Alpha-4 (LAMA4) gene was identified in proband and his 2 brothers with relevant clinical symptoms. Individuals without carrying this mutation in this family had no symptoms or cardiac structural abnormality related to DCM or conduction system disease. The p.G218R mutation is located in a conservative area within the laminin epidermal growth factor (EGF)-like domain of LAMA4 with uncertain significance in ClinVar archive. Bioinformatic analysis predicted p.G218R mutation as deleterious and pathogenic damaging in DCM patients. Our results reported a potential pathogenic mutation associated with DCM, which may provide further insight into genetic contributions of LAMA4 gene mutations to DCM phenotypes.
扩张型心肌病（DCM）的特征是心室扩张和收缩功能不佳。在家族性或明显散发的特发性DCM病例中，约有一半归因于遗传原因，据报道有50多个基因可导致DCM。然而，大多数DCM患者的遗传基础仍然未知，需要进一步研究。在中国一个患有DCM和传导系统疾病的家族中，从先证者及其家庭成员那里收集了临床数据、家族史和血样。使用下一代测序（NGS）进行了遗传分析。进行了生物信息学分析以预测基因突变的致病后果。在先证者及其2名有相关临床症状的兄弟中，发现了层粘连蛋白α-4（LAMA4）基因的错义杂合突变c.652G>A（p.G218R）。该家族中未携带此突变的个体没有与DCM或传导系统疾病相关的症状或心脏结构异常。p.G218R突变位于LAMA4的层粘连蛋白表皮生长因子（EGF）样结构域内的一个保守区域，在ClinVar档案库中的意义不确定。生物信息学分析预测p.G21,8R突变对DCM患者有害且具有致病破坏性。我们的结果报告了一个与DCM相关的潜在致病突变，这可能为进一步了解LAMA4基因突变对DCM表型的遗传贡献提供线索。
