Functional analysis of <i>MITF</i> gene mutations associated with Waardenburg syndrome type 2

Luo, Hunjin; Chen, Hongsheng; Mei, Lingyun; He, Chufeng; Jiang, Lu; Li, Jia‐Da; Feng, Yong

doi:10.1016/j.febslet.2012.10.006

Cited by 23 publications

(27 citation statements)

References 25 publications

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“…The results show that (Figure 2a) WT MITF improved the TYR promoter activity up to 17-fold, consistent with previous reports; 23, 24 however, X420Y MITF only induced threefold increase.…”

Section: Resultssupporting

confidence: 92%

“…24 Furthermore, the nonstop mutation will introduce a number of amino acids with novel properties to a protein’s C terminus. 35 Extremely hydrophobic residues might have a greater impact.…”

Section: Discussionmentioning

confidence: 99%

“…23, 24 The nonstop mutation (p.X420Y) introduced 33 extra amino-acid residues (YRILPALHSHKLLPFLIRRFNNLPEGVFLIIFL) to the C terminus of MITF, which was introduced by PCR and cloned into pCMV-3 × Flag. 24 The sequences were reviewed by direct nucleotide sequencing.…”

Section: Methodsmentioning

confidence: 99%

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Functional analysis of a nonstop mutation in MITF gene identified in a patient with Waardenburg syndrome type 2

et al. 2017

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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.

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“…The results show that (Figure 2a) WT MITF improved the TYR promoter activity up to 17-fold, consistent with previous reports; 23, 24 however, X420Y MITF only induced threefold increase.…”

Section: Resultssupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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Functional analysis of a nonstop mutation in MITF gene identified in a patient with Waardenburg syndrome type 2

et al. 2017

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“…Causative mutations in MITF are mostly recognized to be involved in metabolic disorders in melanocytes, affecting the pigment content of the skin, hair, and eyes. Moreover, in eyes, the microphthalmia-associated transcription factor plays a role in the development of retinal pigment epithelial cells (Zhang et al, 2012).…”

Section: The Microphthalmia-associated Transcription Factormentioning

confidence: 99%

Genetic background of coat colour in sheep

et al. 2018

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Abstract. The coat colour of animals is an extremely important trait that affects their behaviour and is decisive for survival in the natural environment. In farm animal breeding, as a result of the selection of a certain coat colour type, animals are characterized by a much greater variety of coat types. This makes them an appropriate model in research in this field. A very important aspect of the coat colour types of farm animals is distinguishing between breeds and varieties based on this trait. Furthermore, for the sheep breeds which are kept for skins and wool, coat/skin colour is an important economic trait. Until now the study of coat colour inheritance in sheep proved the dominance of white colour over pigmented/black coat or skin and of black over brown.

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“…; Zhang et al . ). In contrast, mutations leading to the more severe phenotype in Tietz syndrome in human and to the German white Fleckvieh syndrome in cattle are described to have a dominant negative effect, through interaction of the mutated protein with the wild‐type allele product (Smith et al .…”

mentioning

confidence: 97%

A 19‐Mb de novo deletion on BTA 22 including MITF leads to microphthalmia and the absence of pigmentation in a Holstein calf

Wiedemar

Drögemüller

2014

Animal Genetics

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Mutations in MITF lead to a large variety of phenotypes in human, mice and other species. They mostly affect pigmentation and hearing, whereas in mice, they may additionally cause microphthalmia and osteopetrosis. In this study, we report a single case of a Holstein calf with lack of pigmentation and microphthalmia born to healthy parents. Mendelian analysis of high-density SNP genotypes reveals a large number of parentage errors showing missing paternal alleles in the offspring, indicating a deletion encompassing 19 Mb on BTA 22. The genomic deletion affects the paternal allele and includes MITF and 131 other annotated genes. As the calf shows only one copy of the BTA 22 segment, the observed phenotype is probably caused by haploinsufficiency of the genes in that genomic region. Both the observed lack of skin pigmentation and reduced eye size can most likely be explained by a lack of MITF function.

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Functional analysis of MITF gene mutations associated with Waardenburg syndrome type 2

Cited by 23 publications

References 25 publications

Functional analysis of a nonstop mutation in MITF gene identified in a patient with Waardenburg syndrome type 2

Functional analysis of a nonstop mutation in MITF gene identified in a patient with Waardenburg syndrome type 2

Genetic background of coat colour in sheep

A 19‐Mb de novo deletion on BTA 22 including MITF leads to microphthalmia and the absence of pigmentation in a Holstein calf

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