title: Functional analysis of a nonstop mutation in MITF gene identified in a patient with Waardenburg syndrome type 2.
abstract: Waardenburg syndrome (WS) is an autosomal dominant inherited neurogenic disorder with the combination of various degrees of sensorineural deafness and pigmentary abnormalities affecting the skin, hair and eye. The four subtypes of WS were defined on the basis of the presence or absence of additional symptoms. Mutation of human microphthalmia-associated transcription factor (MITF) gene gives rise to WS2. Here, we identified a novel WS-associated mutation at the stop codon of MITF (p.X420Y) in a Chinese WS2 patient. This mutation resulted in an extension of extra 33 amino-acid residues in MITF. The mutant MITF appeared in both the nucleus and the cytoplasm, whereas the wild-type MITF was localized in the nucleus exclusively. The mutation led to a reduction in the transcriptional activities, whereas the DNA-binding activity was not altered. We show that the foremost mechanism was haploinsufficiency for the mild phenotypes of WS2 induced in X420Y MITF.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Hunan, People's Republic of China.|Department of Otolaryngology, First Affiliated Hospital, Xinjiang Medical University, Xinjiang, People's Republic of China.|Province Key Laboratory of Otolaryngology Critical Disease, Xiangya Hospital, Central south University, Hunan, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Center Laboratory, Taiyuan Central Hospital, Shanxi, People's Republic of China.
authors.forename: Ziqi
authors.initials: Z
authors.lastname: Hao
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Hunan, People's Republic of China.
authors.forename: Hunjin
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Hunan, People's Republic of China.|Province Key Laboratory of Otolaryngology Critical Disease, Xiangya Hospital, Central south University, Hunan, People's Republic of China.
authors.forename: Chufeng
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Hunan, People's Republic of China.|Province Key Laboratory of Otolaryngology Critical Disease, Xiangya Hospital, Central south University, Hunan, People's Republic of China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Mei
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Hunan, People's Republic of China.|Province Key Laboratory of Otolaryngology Critical Disease, Xiangya Hospital, Central south University, Hunan, People's Republic of China.
authors.forename: Yalan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Hunan, People's Republic of China.|The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
authors.forename: Xueping
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Hunan, People's Republic of China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Niu
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Hunan, People's Republic of China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Hunan, People's Republic of China.
authors.forename: Jia-Da
authors.initials: JD
authors.lastname: Li
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Hunan, People's Republic of China.|Province Key Laboratory of Otolaryngology Critical Disease, Xiangya Hospital, Central south University, Hunan, People's Republic of China.|Department of Center Laboratory, Taiyuan Central Hospital, Shanxi, People's Republic of China.|State Key Laboratory of Medical Genetics, Central South University, Hunan, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Feng
mesh_terms: D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics*; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D041681:NIH 3T3 Cells; D013347:Subcellular Fractions / Q000378:metabolism; D014158:Transcription, Genetic; D014849:Waardenburg Syndrome / Q000235:genetics*; D055815:Young Adult
chemical_list: C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D050505:Mutant Proteins; D004247:DNA