Multiple genetic variants in adolescent patients with left ventricular noncompaction cardiomyopathy. (1st March 2020)

• Record Type: Journal Article
• Authors: Liu, Shenghua; Xie, Yuanyuan; Zhang, Hongliang; Feng, Zongqi; Huang, Jian; Huang, Jie; Hu, Shengshou; Wei, Yingjie
• Is Part Of: International journal of cardiology. Volume 302(2020)
• Page Start: 117
• Page End: 123
• Publication Date: 2020-03-01
• Subjects: Left ventricular noncompaction cardiomyopathy -- Exome sequencing -- Genetics; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2019.12.001
• Languages: English
• ISSNs: 0167-5273

Abstract

Abstract: Background: Left ventricular noncompaction cardiomyopathy (LVNC) is a primary cardiomyopathy with an unclear aetiology. The clinical symptoms range from asymptomatic to heart failure, arrhythmias and sudden cardiac death. This study aimed to characterize the genetic features and clinical outcomes of LVNC who underwent heart transplantation (HTx) to reveal the potential genetic pathogenesis. Methods and results: We recruited 16 cases who underwent HTx in our hospital. Exome-sequencing was performed to reveal genetic background. Clinical information and histopathology features of patients were investigated. Gene expression profiling of tissue fibrosis were evaluated by quantitative PCR. The median age of patients was 21 years. Of the 16 patients, 14 harboured multiple gene variants involved in LVNC. Ten of the patients harboured biallelic variants and/or truncating variants. Young patients (<18) with biallelic variants and/or truncating variants and lower LVEF (<45%) at initial symptom deteriorated quickly. Except for noncompaction myocardium, myocardial fibrosis was a remarkable pathological feature, and gene profiles related to immune inflammation and extracellular matrix remodelling were upregulated. Conclusions: This study showed that multiple pathologic variants were underlie genetic mechanism of LVNC who in high risks, suggesting that genetic screening should be applied to the diagnosis of LVNC. LVNC patient with multiple variants should be considered carefully follow-up. Genetics involved in the phenotype and cardiac fibrosis, and is the major causing for LVNC. Highlights: The genetics and clinical features of a cohort of LVNC patients with severe symptom who underwent HTx were described. Multiple gene variants synergistically function in the phenotype of LVNC who was in high cardiac risk. Patients with biallelic-variants and truncating variants in cardiac genes should be considered carefully follow-up. Pathological variants induced to abnormal contraction of cardiac myocytes involved in the pathological progress of LVNC.