title: Functional analysis of MITF gene mutations associated with Waardenburg syndrome type 2.
abstract: 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.
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Hunjin
authors.initials: H
authors.lastname: Luo
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Chen
authors.forename: Lingyun
authors.initials: L
authors.lastname: Mei
authors.forename: Chufeng
authors.initials: C
authors.lastname: He
authors.forename: Lu
authors.initials: L
authors.lastname: Jiang
authors.forename: Jia-Da
authors.initials: JD
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Feng
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D041681:NIH 3T3 Cells; D014849:Waardenburg Syndrome / Q000235:genetics* / Q000378:metabolism
chemical_list: D051739:Microphthalmia-Associated Transcription Factor