Abstract 13176: Overexpression of BANF1 is Linked to Cardiac Pathologies in Progeria Patients

Introduction: Hutchinson-Gilford progeria (HGP) is a genetic disorder caused by a single nucleotide mutation in the Lamin A gene. This mutation causes the production of the abnormal lamin A protein called progerin. Children affected by this disorder age rapidly and die at an early age, mostly from cardiac pathologies. Another similar progeroid syndrome is Nestor-Guillermo progeria, in which the patients exhibit accelerated aging but have a longer life span. This latter syndrome is caused by a mutation that silences the BANF1 gene. Hypothesis: We hypothesize that BANF1 is linked to cardiovascular disease in Hutchinson-Gilford progeria patients. This gene could be targeted to reduce cardiac pathologies and increase the lifespan of patients with HGP. Methods: We obtained skin fibroblasts from two HGP patients and their respective parents from the Progeria Foundation. We successfully reprogrammed the fibroblasts into induced pluripotent stem cells by a safe non-viral method and further differentiated them into induced cardiomyocytes (iCMCs). Then, we performed multiple analyses to compare the iCMCs of the patients, their parents, and control iCMCs. Results: Through in-silico protein analysis, we were able to identify a relationship between nuclear lamina proteins and BANF1, which is also correlated to cardiac-specific proteins GATA4 and NKX2.5 ( Figure A ). Additionally, through qPCR ( Figure B ) and Western Blot ( Figure C ) analyses, we identified a significant difference in BANF1 expression between the progeria patient iCMCs and the other iCMCs. BANF1 was overexpressed in patient iCMCs, whereas, it had normal expression in patient fibroblasts when compared to control cells. Conclusions: We believe that BANF1 could be a good target for future therapeutic approaches to minimize cardiac pathologies in HGP patients and extend their lifespan.