Sickle cell disease in pregnancy – a rare condition with detrimental outcome: a case report

Sickle cell disease (SCD) in pregnancy is uncommon in Malaysia. We present a case of sickle cell disease in pregnancy with maternal and fetal complications. The patient presented with acute pain crisis and hemolysis in the third trimester. Despite thromboprophylaxis, she developed deep vein thrombosis. The pregnancy was further complicated by severe pre-eclampsia and intrauterine growth restriction which require preterm caesarean section. The baby was admitted to Neonatal Intensive Care Unit due to prematurity and low birth weight. Multidisciplinary approach in managing pregnant patient with SCD is essential in achieving good obstetrics outcome

Cardiomyocyte-specific conditional knockout of the histone chaperone HIRA in mice results in hypertrophy, sarcolemmal damage and focal replacement fibrosis

HIRA is the histone chaperone responsible for replication-independent incorporation of histone variant H3.3 within gene bodies and regulatory regions of actively transcribed genes, and within the bivalent promoter regions of developmentally regulated genes. The HIRA gene lies within the 22q11.2 deletion syndrome critical region; individuals with this syndrome have multiple congenital heart defects. Because terminally differentiated cardiomyocytes have exited the cell cycle, histone variants should be utilized for the bulk of chromatin remodeling. Thus, HIRA is likely to play an important role in epigenetically defining the cardiac gene expression program. In this study, we determined the consequence of HIRA deficiency in cardiomyocytes in vivo by studying the phenotype of cardiomyocyte-specific Hira conditional-knockout mice. Loss of HIRA did not perturb heart development, but instead resulted in cardiomyocyte hypertrophy and susceptibility to sarcolemmal damage. Cardiomyocyte degeneration gave way to focal replacement fibrosis and impaired cardiac function. Gene expression was widely altered in Hira conditional-knockout hearts. Significantly affected pathways included responses to cellular stress, DNA repair and transcription. Consistent with heart failure, fetal cardiac genes were re-expressed in the Hira conditional knockout. Our results suggest that transcriptional regulation by HIRA is crucial for cardiomyocyte homeostasis