BACKGROUND: Kabuki syndrome is a haploinsufficient congenital multi-organ 
malformation syndrome, which frequently includes severe heart defects. Mutations 
in the histone H3K4 methyltransferase KMT2D have been identified as the main 
cause of Kabuki syndrome, however, the role of KMT2D in heart development 
remains to be characterized.
RESULTS: Here we analyze the function of Kmt2d at different stages of Xenopus 
heart development. Xenopus Kmt2d is ubiquitously expressed at early stages of 
cardiogenesis, with enrichment in the anterior region including the cardiac 
precursor cells. Morpholino-mediated knockdown of Kmt2d led to hypoplastic 
hearts lacking the three-chambered structure. Analyzing different stages of 
cardiogenesis revealed that development of the first and second heart fields as 
well as cardiac differentiation were severely affected by loss of Kmt2d 
function.
CONCLUSION: Kmt2d loss of function in Xenopus recapitulates the hypoplastic 
heart defects observed in Kabuki syndrome patients and shows that Kmt2d function 
is required for the establishment of the primary and secondary heart fields. 
Thus, Xenopus Kmt2d morphants can be a valuable tool to elucidate the etiology 
of the congenital heart defects associated with Kabuki syndrome.