MITF mutations results in an abnormal melanocyte development and lead to 
Waardenburg syndrome type 2 (WS2). Here, we analyzed the in vitro activities of 
two recently identified WS2-associated MITF mutations (p.R217I and p.T192fsX18). 
The R217I MITF retained partial activity, normal DNA-binding ability and nuclear 
distribution, whereas the T192fsX18 MITF failed to activate TYR promoter and 
showed aberrant subcellular localization which may be caused by deletion of 
nuclear localization signal (NLS) at aa 213-218 (ERRRRF). These results suggest 
that haploinsufficiency may be the underlying mechanism for the mild phenotypes 
of WS2 caused by these two mutations.