Functional Analysis of Human Genetic Variants Using Zebrafish

Utilizing zebrafish as a model organism, this study investigates the genetic factors con- tributing to congenital heart defects (CHD) and cardiomyopathy (CM). Zebrafish offer unique advantages in cardiovascular research, such as optical transparency and rapid development, making them well-suited for studying developmental processes and disease pathogenesis. Molecular cytogenetic techniques identified novel variants in the PRDM16 gene associated with ARVC. Additionally, ES (Exome sequencing) identified variants in the CAPZβ gene linked to patients with CHD. Functional analysis in zebrafish embryos revealed phenotypic similarities to human disease, implicating CAPZβ as a candidate gene for CHD and PRDM16 in ARVC. Specifically molecular cytogenetic techniques identified four novel variants in the PRDM16 gene in patients with ARVC and ES led to the identification of four novel variants in the CAPZβ gene among patients with CHD. Functional analysis in zebrafish embryos revealed that the CAPZβ-Ser192Asn variant led to impaired cardiac contractility and morphological defects resembling aspects of human CHD phenotypes.