Approved Research

Genetic and clinical characterization of hypertrophic cardiomyopathy (HCM) and genocopies

Lay summary

Hypertrophic cardiomyopathy (HCM) is one of the most common inherited cardiovascular disorders, with an estimated population prevalence of 1:200-1:500. It is recognized to be a common cause of sudden death, and can lead to heart failure and atrial fibrillation. With a complicated pathophysiology and heterogeneous clinical profile, HCM is frequently misunderstood, and often underrecognized in clinical practice. Multiple researches have shown that pathogenic variants in sarcomere genes are the most common genetic aetiology of HCM. In addition, variants in genes associated with left ventricular hypertrophy (LVH) can cause a phenotype mimicking HCM, which are usually referred to as HCM mimickers or genocopies, including Fabry disease, familial amyloidosis, Noonan syndrome, Danon disease and glycogen storage disease. Since these defective genes and its mutation types determine the disease course, discovering genes associated with HCM are crucial for developing better treatment and accurate risk prediction. The main purpose of this project is to explore unknown pathogenic variants that account for the aetiology of HCM, and investigate the relationship between multiple risk factors and outcomes of HCM and genocopies. Through integration and analysis of extensive clinical, genetic, imaging and life style data in UK biobank, we aim to better understand the genetic basis of HCM and its genocopies, in order to improve the accuracy of diagnosis and develop new treatments based on their genotypes. The project duration is 3 years. Our research will provide more evidence-based recommendations to improve clinical management of HCM and genocopies, with the aim of reducing mortality and disability.