We report a case of congenital cytomegalovirus and Herpes simplex virus infection suspected via ultrasound indicated by the presence of fetal cerebral abnormalities. The pregnancy was electively terminated at 31 weeks of gestation. The postmortem examination of the foetus showed brain with lissencephaly. The histopathological examination revealed numerous enlarged cells containing cytomegalic inclusions and multinucleated giant cells in multiple fetal organs and placenta. Documented evidence of histopathological detection of cytomegalovirus inclusions in multiple organs are very sparse in literature. This case highlights the causal relationship of viral infections in early pregnancy and abnormalities of the central nervous system.
Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease (CKD). Here we show that recessive mutations in FAT1 cause a distinct renal disease entity in four families with a combination of SRNS, tubular ectasia, haematuria and facultative neurological involvement. Loss of FAT1 results in decreased cell adhesion and migration in fibroblasts and podocytes and the decreased migration is partially reversed by a RAC1/CDC42 activator. Podocyte-specific deletion of Fat1 in mice induces abnormal glomerular filtration barrier development, leading to podocyte foot process effacement. Knockdown of Fat1 in renal tubular cells reduces migration, decreases active RAC1 and CDC42, and induces defects in lumen formation. Knockdown of fat1 in zebrafish causes pronephric cysts, which is partially rescued by RAC1/CDC42 activators, confirming a role of the two small GTPases in the pathogenesis. These findings provide new insights into the pathogenesis of SRNS and tubulopathy, linking FAT1 and RAC1/CDC42 to podocyte and tubular cell function.