This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison
What is Waardenburg Syndrome?
Waardenburg syndrome (WS) is a rare autosomal dominant syndrome that affects the auditory system and causes pigmentation abnormalities in hair, skin, and eyes [1]. WS type 2a (WS2A) is affected by the MITF gene [1]. There are four different types of Waardenburg syndrome that range in different severities of symptoms, however the other 3 are influenced by other genes and will not be studied here. The main symptoms of WS2A can include a patch of white hair in the front hairline, full or partial hearing loss, and brilliant blue coloring of one eye (heterochromia iridis) or both eyes [1]. Even within WS2A there are varying degrees of the syndrome, therefore not all cases will be the same.
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MITF gene
Gene Location: 3p13
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MITF (microphthalmia-associated transcription factor) is located on chromosome 3 and has been associated with WS2A cases. MITF converts fibroblasts into melanocytes, a mature melanin-forming cell, and is involved in the differentiation of these cells [2]. When mutated there is a loss of function of these genes and it results in reduced pigmentation, as seen in the hair and eyes of those affected by WS2A. It has been shown that the mutated MITF gene loses the ability to bind to the promoter, therefore the necessary genes for the melanocyte cell differentiation cannot be activated [2].
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How is WS2A inherited?
WS2A is an autosomal dominant syndrome, meaning only one copy of the gene needs to be mutated for the symptoms to be present. If at least one parent has the mutated gene copy, it is likely that 50% of the children will also be affected. When both parents are affected by WS2A it is likely that 75-100% of the children will be affected, depending if both parents carry one or two mutated copies of the genes.
It has been shown for WS2A that when only one copy of the gene is mutated, the normal copy of the gene is still capable of doing its job [2]. However, because there are still symptoms showing, the one normal copy of the gene is not enough to make adequate amounts of the necessary protein, this is known as haploinsufficiency. |
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References
1. Shi, Y., Li, X., Ju, D., Li, Y., Zhang, X., & Zhang, Y. (2016). A novel mutation of the MITF gene in a family with Waardenburg syndrome type2: A case report. Experimental and Therapeutic Medicine. doi:10.3892/etm.2016.3042
2. Tachibana, M. (1997). Evidence to Suggest That Expression of MITF Induces Melanocyte Differentiation and Haploinsufficiency of MITF Causes Waardenburg Syndrome Type 2A. Pigment Cell Research,10(1-2), 25-33. doi:10.1111/j.1600-0749.1997.tb00462.x
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1. Shi, Y., Li, X., Ju, D., Li, Y., Zhang, X., & Zhang, Y. (2016). A novel mutation of the MITF gene in a family with Waardenburg syndrome type2: A case report. Experimental and Therapeutic Medicine. doi:10.3892/etm.2016.3042
2. Tachibana, M. (1997). Evidence to Suggest That Expression of MITF Induces Melanocyte Differentiation and Haploinsufficiency of MITF Causes Waardenburg Syndrome Type 2A. Pigment Cell Research,10(1-2), 25-33. doi:10.1111/j.1600-0749.1997.tb00462.x
Images
Banner: http://www.africapublic.com/girl-with-ocean-eyes/
Destiny Baars | [email protected]
University of Wisconsin - Madison www.genetics564.weebly.com Last updated: 5/11/2017 |
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