Presentation description

1p36 deletion syndrome is one of the most common congenital genetic disorders present in nearly 1 in 5,000 births. 1p36 deletion syndrome can include deleting the positive regulatory domain containing 16 (PRDM16), a transcription coregulator whose absence is strongly correlated in rodents and humans with cardiomyopathies. Without treatment cardiomyopathy leads to heart failure, however, there is a stark difference between phenotypic outcomes when it comes to female and male patients with 1p36 deletion syndrome who lost PRDM16: female patients experience earlier onset of and more aggressive cardiomyopathies with reduced survival rates.
Our lab hypothesizes that the deletion of PRDM16 produces downstream sex-specific patterns of replication stress and DNA damage during cardiac development that may significantly contribute to differences in cardiac function, and metabolic maturation leading to the phenotypic differences in cardiomyopathy.
Our lab isolated and cultured neonatal rat ventricular cardiomyocytes and rat cardiomyoblasts (H9C2s) to investigate PRDM16's role in replication stress and DNA damage. In both cell types, we observed higher DNA damage and lower DNA repair in female KO using siRNA. We will use western blots and Immunofluorescence to analyze our collected cells for replication stress and DNA damage using specific antibodies. We expect seeing sex-specific patterns of replication stress and DNA damage in both cells.
Exploring sex-differentiated cardiac maturation is imperative to understanding PRDM16's role in cardiac development and developing precise therapeutics tailored to individual patients with 1p36 deletion syndrome.