A potential pathogenic mutation of LAMA4 in a Chinese family with dilated cardiomyopathy and conduction system disease

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.