Functional analysis of a nonstop mutation in MITF gene identified in a patient with Waardenburg syndrome type 2.
J Hum Genet
; 62(7): 703-709, 2017 Jul.
Article
em En
| MEDLINE
| ID: mdl-28356565
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Waardenburg
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Fator de Transcrição Associado à Microftalmia
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Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article