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Functional analysis of MITF gene mutations associated with Waardenburg syndrome type 2
Author(s) -
Zhang Hua,
Luo Hunjin,
Chen Hongsheng,
Mei Lingyun,
He Chufeng,
Jiang Lu,
Li Jia-Da,
Feng Yong
Publication year - 2012
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2012.10.006
Subject(s) - microphthalmia associated transcription factor , haploinsufficiency , waardenburg syndrome , pax3 , phenotype , nuclear localization sequence , biology , mutation , genetics , gene , microbiology and biotechnology , transcription factor
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.