If you’re currently undergoing testing for systemic mastocytosis (SM), you might have heard of the KIT D816V mutation. Over 90% of patients with SM will test positive for this mutation, making it an important diagnostic factor for the disease.
What is the KIT gene?
The KIT gene codes for a type of protein called a receptor tyrosine kinase, which helps carry messages into your body’s cells. In the case of the KIT protein, also known as CD117, these messages tell the cells to grow, divide and move.
The mast cells of most patients with SM carry KIT gene mutations that interfere with these signaling pathways. As a result, the receptors remain permanently in the “on” position, causing the buildup of mast cells in the body. This overactivation of mast cells contributes to the symptoms of SM, which include:
- Allergic events.
- Flushing.
- Dizziness.
- Low blood pressure.
- Abdominal pain.
The most common KIT mutation is the D816V mutation. This means that at the 816th position of the KIT protein, the building block aspartate is replaced with valine. Though it may be hard to believe, this one miniscule change is responsible for triggering the onset of symptoms.
KIT mutations are typically not inherited, although there have been a few reported cases of the disease running in families.
Read more about SM testing and diagnosis
How is KIT D816V mutation testing performed?
KIT D816V mutation testing is simple — all it takes is a blood draw, though bone marrow can also be used. Once the sample is collected, it will be sent to a lab that uses sequencing technology to detect whether a mutation is present.
These tests aren’t always perfect, however. Some patients might test negative using the traditional methods but are found to harbor the mutation using more advanced mutation-detecting tools. This could happen, for example, if the sample has a relatively low number of cells carrying the mutation. Therefore, an SM diagnosis is made on the basis of many different criteria — including symptoms, imaging and biopsies — and not on genetic testing alone.
What happens if you test negative for the D816V mutation?
If you don’t have the KIT D816V mutation, it isn’t necessarily the end of the road. A small subset of individuals with SM have other mutations in the KIT gene or mutations in other genes altogether. These include TET2, SRSF2, ASXL1 and RUNX1.
It’s also possible to meet the diagnostic criteria for SM without testing positive for any mutations. In fact, having a KIT gene mutation is only considered a minor criterion for SM, meaning that while it can help to confirm a diagnosis, it isn’t necessary.
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