Clinical Testing for Genetic Mutations
Genetic testing is most likely to identify mutations in individuals who have either:
- multiple CCM lesions that can’t be explained by a developmental venous anomaly (also known as venous angioma) or by a history of brain or spinal radiation.
- and/or a family history of CCM.
Genetic testing is unlikely to identify mutations in individuals with sporadic CCM (single lesions with no family history) or lesions that are clustered around a developmental venous anomaly. The cause of sporadic CCM remains unknown, but it is not believed to be due to inheritable mutations.
The standard strategy for genetic testing is to begin by sequencing the CCM1 gene. This is because mutations in the CCM1 gene are most common (seen in at least 53% of all CCM families). If no mutation is identified, CCM2 then CCM3 will be sequenced. CCM2 gene mutations account for at least 15%, and CCM3 mutations account for roughly 10%, of familial CCM cases. For particular subgroups at high risk for founder mutations, a specific mutation of a gene may be tested first.
Clinical vs Research Testing
Testing for genetic mutations may be for research or clinical purposes. Because of its strict regulation, only clinical testing can be used to make a diagnosis of a genetic mutation. Research testing (that which you get when you enroll in a study) must be verified by a clinical test before it is considered to be a formal diagnosis. For this reason, specific research results are not typically given to the study participant. Instead, he or she may be recommended to have clinical testing done.
Where to Have Testing
There are multiple labs in the United States, listed below, that offer CCM genetic testing. Unless you already know which mutation runs in your family or are a member of a group at risk for a founder mutation, you will have all 3 genes (CCM1, CCM2, CCM3) tested as part of your genetic testing. Direct-to-consumer products like those offered by 23andMe or Ancestry do not include tests for all 3 CCM genes. For all CCM testing, a doctor must be involved. Testing may be performed using a blood sample or a saliva sample, depending on the requirements of the lab.
ARUP Laboratories (Vascular Panel)
What to Know Before You Test
Genetic testing can only rule in a mutation; it cannot rule out one. This means that a negative result does not necessarily mean that a genetic mutation does not exist. This is because there are ways that a gene can mutate that are not picked up by testing. Current testing methods that include sequencing, copy number variant, and large deletion testing are able to produce a result for about 95% of familial cases but not all.
If a genetic mutation is identified, it can make it affordable for your family to be screened for the mutation. Rather than going through an MRI, other family members can submit saliva, or in some cases simple cheek swabs, for “CCM Known Mutation Detection.”
Genetic testing can yield potentially upsetting results. Please make certain that you have the necessary support –a genetic counselor or a very knowledgeable and compassionate doctor – before beginning this process.
GeneReviews eBook; Cerebral Cavernous Malformation, Familial http://www.ncbi.nlm.nih.gov/books/NBK1293/
Page last updated 03.13.20