A presentation by Rachel Dos Santos

Brief Summary

Heterochromia iridis is a condition characterized by abnormalities of the iris (the colored part of the eye), specifically within the stroma. In people affected by complete heterochromia, the iris of one eye is a different color than the iris of the other eye. Segmental heterochromia occurs when areas of the same iris are different in color. Heterochromia iridium (two different-colored eyes within a single individual) and heterochromia iridis (a variety of color within a single iris) are relatively rare in humans and result from increased or decreased pigmentation of the iris, which is deciphered by cells known as melanocytes.

Where is the gene located?

Microphthalmia-associated transcription factor (MITF) is a gene/transcription factor that helps control the development and function of pigment-producing cells called melanocytes. The melanocytes of the iris rest in a richly innervated psuedosyncytium, which is necessary to maintain eye color. Two genes control eye color: EYCL3, found on chromosome 15, which codes for brown/blue eye color (BEY), and EYCL1, found on chromosome 19, which codes for green/blue eye color (GEY).

The BEY gene and GEY gene is now known as OCA2, which can be controlled in chromosome 15 of the cell.

What kind of mutation causes Heterochromia?

Let's say there is a gene X. At the start of gene X is a series of DNA letters that looks like this:


Now there is a protein found in the stroma that likes to sit on AGTC. There is one of these in front of gene X so the protein sits there. This protein tells the cell that this is a gene and to start reading.

Now imagine that someone has this DNA in front of gene X:


Now our protein has nowhere to sit and so is not in front of gene X. The result is that the cell doesn't recognize the start of gene X anymore so gene X is not turned on in this cell.

But this change would not affect another protein that likes GACTG. It can still sit on the DNA and mark the gene for the cell. So any cell that has this protein could still turn gene X on.

This type of mutation would be classified as a missense substitution point mutation.

This is presumably what is happening with OCA2 and blue eyes. The 3 identified changes are outside of the part of the gene that is read. So the changes may cause a protein in the stroma to no longer sit on the DNA. Now the machinery in the stroma cells doesn't see the gene and you have blue eyes.

Now, for heterochromia to happen, the rate of which melanocytes produce pigmentation is not constant with both eyes. With nervous signals from the brain as well as the genes and gene control, one eye would produce more pigmentation than the other, thus making one eye brown and the other blue, or one eye blue and the other brown (both of these occurances are more common than other combinations). As for gene control, another aspect would be that if the sequence for where the protein would originally sit on is different, it would activate another protein which would start coding for the gene for blue eyes.

The Function of the Genes

The OCA2 gene (formerly called the P gene) provides instructions for making a protein called the P protein (no other name). This protein is located in melanocytes, which are specialized cells that produce a pigment called melanin. Melanin is the substance that gives skin, hair, and eyes their color, in the general sense.

These P proteins, when effected by the mutation, has little difference on the structure of the protein the gene codes for. Referring back to the gene X example in the "What kind of mutation causes Heterochromia?", a specific sequence has to appear in order for this P protein to come into effect in the OCA2 gene and begin being produced. If there was a missense substitution point mutation, the only effect there is is that this P protein cannot produce the same quantitative amount of melanin, therefore resulting in blue eyes. For Heterochromia, these two genes would differ in which one eye has the proper sequence while the other eye doesn't. Therefore, there'll be more production of melanin due to these melanocytes in one eye and the other would not produce at the same uniform rate.

What is the mechanism of the disorder?

What effects does the alteration in function of the protein have on the workings of the cell and the body, you may ask? Well, there's no alternation. As mentioned before, without the proper coding sequence, the P protein cannot produce these melanin pigments at often as if there was the proper coding sequence. With two eyes producing melanin at different rates in melanocytes, the one eye that is producing a low amount of melanin will be a factor of the product of blue eyes, whereas the one eye that's producing melanin within the melanocytes at the fast constant rate will produce brown eyes.

Symptoms of the disorder?

Heterochromia Iridum (Iridis) is a genetic disorder, which most cases are isolated and sporadic, resulting from an alternation in the sequences within the genes, as mentioned before, within the entire iris or even a particular section. In this case, there aren't any symptoms which are present with this disorder. When looking at well-known syndromes like Waardenburg Syndrome, Sturge-Weber Syndrome, and etc., Heterochromia is indeed one of the most striking features within these disorders, along with many other symptoms that come with the syndromes.


There is no treatment for the disorder, although there have been several articles and websites which state that a possible replacement of the complete iris is possible.

Different Types of Heterochromia

So the first video shows the first type of Heterochromia; one that is more commonly seen and it is called Central Heterochromia (note: the person in this video goes back and forth with showing the eyes, so the main focus is the first 15-20 seconds of the video.

With Sectoral Heterochromia, the iris contains two completely different colors in the same area. Sectoral Heterochromia looks like an irregular spot that is a different color than the eye color.

Complete Heterochromia occurs when the eyes are of two different colors. This is the most dramatic of all the Heterochromia.


Don't it make your brown eyes blue? (n.d.). Retrieved May 22, 2015, from http://genetics.thetech.org/original_news/news39

Heterochromia iridis | Disease | Overview | Office of Rare Diseases Research (ORDR-NCATS). (n.d.). Retrieved May 22, 2015, from https://rarediseases.info.nih.gov/gard/8590/heter...

J. Gross, S. (2001, November 3). How does someone get two different-colored eyes? Retrieved May 22, 2015, from http:/ www.scientificamerican.com/article/how-does-someo...

MITF gene. (n.d.). Retrieved May 22, 2015, from http://ghr.nlm.nih.gov/gene/MITF

Comment Stream

2 years ago

Good explanation of missense mutation! Just make sure to provide in-text citations in your texts. Last source in your bibliography should be in APA format. Well done in your explanation of heterochomia!