A research on the relationship of genotypes and phenotypes in hypertrophic cardiomyopathy

Objective To explore the relationship between genotypes and phenotypes in hypertrophic cardiomyopathy(HCM) patients using whole exome sequencing(WES) and three-dimensional speckle-tracking echocardiography(3D-STE). Methods Twenty patients with apical HCM(ApHCM) and 25 patients with non-apical HCM(non-ApHCM) from June 2018 to January 2019 in Zhongshan Hospital of Fudan University were enrolled. All subjects underwent venous blood sampling and WES. Regular two-dimensional echocardiography was performed to acquire the following parameters: interventricular septum thickness, left ventricular posterior wall thickness, left ventricular end diastolic diameter, left ventricular end systolic diameter, the maximum thickness of left ventricular walls and left ventricular ejection fraction(LVEF). Full volume images were collected and then off-time analyzed with 3D-STE to acquire global longitudinal strain(GLS), global circumferential strain(GCS), twist and torsion. The relationships between above parameters, genotypes and phenotypes of left ventricle were analyzed. Results Mutations were found in 73% of HCM patients.The two most common genes MYBPC3 and MYH7 accounted for 18% and 15% of mutations respectively. KCNEc.79C>T(p.Arg27Cys) and PRKAG2c.905G>A (p.Arg302Gln) were detected in both ApHCM group and non-ApHCM group. In ApHCM group, 60% of patients carried genetic mutations, which was significantly lower than non-ApHCM group(84%)(P=0.041). Compared with non-ApHCM group, GLS in ApHCM group was significantly higher (P=0.008). There was no statistical difference of GLS between patients with mutations and without mutations(P=0.068). GLS demonstrated a moderate correlation with morphologic types of HCM(ApHCM and non-ApHCM)(r=0.364, P=0.012). However, there was no correlation between GLS and the condition of mutations(r=0.269, P=0.062). Conclusions The relationship between genetics and phenotypic expression of HCM appears to be complex and heterogeneous. There are marked differences in gene mutations and systolic functions between ApHCM and non-ApHCM. The value of GLS correlates with the shape of left ventricle but not with genotypes. Key words: Echocardiography, three-dimensional; Speckle tracking imaging; Hypertrophic cardiomyopathy; Mutations; Strain