Left-right patterning defects associated with Axenfield-Rieger syndrome

The transcription factor FOXC1 is a major cause of the autosomal dominant genetic disease Axenfeld-Rieger syndrome (ARS). Most ARS patients suffer from early-onset glaucoma which eventually leads to blindness; however extra-ocular phenotypes are also common. Cardiac septal defects and valve insufficiency arises in 10-15% of FOXC1-associated ARS cases but the etiology is poorly understood. Chrystal et al. have now uncovered a possible mechanism for this cardiac defect – improper left-right patterning of the organ.

Recently published in the journal Genes, this research demonstrates that foxc1 is necessary for correct situs (left-right asymmetry) of the heart and the gut within zebrafish. Mutation of foxc1 leads to a loss of expression of the key left-right patterning gene lefty2 during a critical time in heart development. Consistently, mutation of LEFTY2 in humans is associated with congenital heart defects. This work enforces the importance of checking cardiac health in ARS sufferers, especially where FOXC1 mutations are identified.