cblC is a multiple congenital anomaly syndrome caused by mutations in the MMACHC gene. cblC is characterized by defects in cobalamin (vitamin B12) metabolism, but mild to moderate craniofacial abnormalities have been consistently documented in patients. Mutations in the mouse Mmachc gene are developmentally lethal and therefore, the mechanisms underlying the craniofacial deficits associated with cblC are not completely understood. Here we seek to produce a viable zebrafish model of cblC syndrome with which to understand the function of MMACHC in facial development. Specifically, we will determine whether the facial anomalies present in cblC are associated with the accumulation of toxic metabolites and cobalamin binding. Our studies have the potential to reveal a potentially paradigm shifting function for MMACHC in facial development and will help to prevent and treat metabolically associated craniofacial phenotypes.

R03DE029517

2020-01-01

2022-12-31