In humans, loss-of-function mutations in ZIC3 cause isolated cardiovascular malformations and X-linked heterotaxy, a disorder with abnormal left-right asymmetry of organs.
The Zic3 mouse model provides a novel tool to dissect the mechanistic underpinnings of conduction system patterning and dysfunction and its relationship to cardiovascular malformations, making it a promising model to improve understanding and risk assessment in the clinical arena.
Furthermore, the mutation abolished the synergistic activation between HAND1 and GATA4, another crucial cardiac transcription factors that has been associated with various congenital cardiovascular malformations and DCM.
Human Filamin A gene (FLNA) mutations are associated with classical X-linked bilateral periventricular nodular heterotopia (PNH), featuring contiguous heterotopic nodules, mega cisterna magna, cardiovascular malformations and epilepsy.
Mutations in SMG9, Encoding an Essential Component of Nonsense-Mediated Decay Machinery, Cause a Multiple Congenital Anomaly Syndrome in Humans and Mice.