There has been a lot in the news lately about how California Health officials have ordered 13 genetic testing companies to stop testing California residents. I think many people do not understand why public health officials are concerned about the flood of new genetic tests offered directly to the public. I think I have an example that may illustrate the problem.Cystic Fibrosis (CF) is a devastating disease that is caused by mutations in the CFTR gene. To have CF, you must inherent one mutation from your mother and one from your father, which means that both copies of your CFTR gene do not work properly. If you only have one mutation in your CFTR gene you are called a carrier for CF, which means that while one copy of the CFTR gene isn't up to snuff, you at least have one working copy. The one working copy is enough to prevent you from developing CF symptoms.
But, being a carrier is no picnic because if you were to have a child with a person who was also a carrier, there is a 25% chance that child will have CF. Most CF carriers have no idea that they carry a mutation in their CFTR gene. About 1 in every 30 North American caucasians is a carrier.
So that brings us to the I148T mutation. When researchers were studying the causes of CF, they discovered that there were a significant amount of people that had CF that also had a mutation in the CFTR gene that causes a substitution of a threonine amino acid for an isoleucine at position 148 of the CFTR protein. Hence the name I148T. Researchers made the assumption that the I148T was one of the two mutations that caused the patients' CF.
So, anyone who was found to have the I148T mutation, but did not have CF symptoms was labeled a carrier for CF. The I148T mutation was included in the testing panel for many labs, including mine.
Unfortunately, that isn't the end of the story. As more people were tested, researchers found that there were people who had the I148T mutation with another known mutation, but did not have CF. If the I148T mutation was actually was a disease causing mutation, then these people should definitely have symptoms of CF, but they did not.
What researchers eventually found was that I148T was actually what is called a benign polymorphism, which means that it is a mutation that does not cause disease. What they found was that the disease causing mutation is really a deletion of 6 base pairs at nucleotide number 3199. The mutation is called 3199del6 and just happens to be inherited in high frequency with the I148T mutation.
Long story short: Lots of people were told they were carriers of a CF causing mutation, namely the I148T mutation, when actually, they just carried a benign polymorphism. Time and more information revealed a more complex picture of CF mutations. To this day the I148T is on the CF testing panel in commercial CF testing kits. We used it as a flag to conduct further testing for the 3199del6 mutation.
So the lesson is, just because a mutation is present does not mean it causes disease. Any genetic test has to have a mound of research proving that it has any clinical relevance. A reputable genetic counselor would be able to sift through the data and give you an interpretation of your results.
