There are two types of testing for genetic mutations: research and clinical. Because of its strict regulation, 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.
At this time, there are two laboratories in the USA that are approved to perform clinical testing of the CCM1, CCM2, and CCM3 genes. These are Prevention Genetics and Gene Dx, both are for-profit laboratories. The information below describes the tests that are offered at the time of this posting. The information that your doctor or genetic counselor will need to begin the testing process can be found on the Clinical DNA Testing Services page of the Prevention Genetics website or on the Services page for Gene Dx. These sites provide the specimen and shipping requirements as well as the CPT codes that can be used to bill insurance. Many insurance carriers will cover diagnostic genetic testing. Prevention Genetics does not offer prenatal testing, though GeneDx does offer this service.
Before beginning clinical genetic testing, there are several things to know. First, genetic testing by sequencing the gene can only rule in a mutation; it can not rule out one. This means that a negative result does not necessarily mean that a genetic mutation does not exist. There are two reasons for this. First, this is because there are ways that a gene can mutate that are not picked up by sequencing – follow up testing would be performed if this were suspected. Second, it appears that not all of the genes that can cause hereditary CCM have been discovered at this time.
That said, if you choose to have genetic testing and a genetic mutation is identified, this can make it very affordable for your family to be screened for the mutation. Rather than going through an MRI, other family members can submit blood, or in some cases simple cheek swabs, for “CCM Known Mutation Detection” or “KRIT1 Common Hispanic Mutation Detection” sequencing.
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.
Prevention Genetics Testing Available
Note: Only 1 blood sample is required to run all tests.
For additional information about each test, see the Clinical DNA Testing Services page of the Prevention Genetics website.
Cerebral Cavernous Malformation 1 (CCM1) KRIT1 exon 10 “Common Hispanic” Mutation Detection.
The identical KRIT1 mutation is common to many Hispanic families affected with CCMs.
KRIT1/CCM1 “Common Hispanic” Mutation Test by Sequencing KRIT1 exon 10
Cerebral Cavernous Malformation 1 (CCM1) KRIT1 Mutation Detection by Sequencing.
Other CCM1 kindreds harbor other mutations in other exons of the KRIT1 gene. Identification of these other mutations has potential clinical significance for presymptomatic diagnosis of CCM in this population and their families.
KRIT1/CCM1 Mutation Test by Sequencing the 16 KRIT1 gene exons
Cerebral Cavernous Malformation 2 (CCM2) MGC4607 Mutation Detection by Sequencing.
In families where no KRIT1/CCM1 mutations are shown, CCM2 testing is available.
MGC4607/CCM2 Mutation Test by Sequencing the 10 MGC4607 gene exons
Cerebral Cavernous Malformation 2 (CCM2) MGC4607 Exon 2-10 Deletion Detection
Cerebral Cavernous Malformation 3 (CCM3) PDCD10 Mutation Detection by Sequencing.
A clinical test for the CCM3 gene is available.
PDCD10/CCM3 Mutation Test by Sequencing 7 PDCD10 gene exons
Cerebral Cavernous Malformation CCM Known Gene Mutation Detection by Sequencing.
In patients where a specific mutation has been demonstrated in a family member, testing will focus on sequencing the exon where the known mutation has been observed.
Accreditation Info. CLIA ID #: 52D1027685 (expires 1/18/07) (CAP#: 7185561, AU ID: 1407125 expires 12/20/08)
Attn: Diagnostics Lab
PreventionGenetics LLC
3700 Downwind Drive
Marshfield, WI 54449 USA
Dr. James Weber
Contact: 715-387-0484
FAX: 715-384-3661
clinicaltesting@preventiongenetics.com
Gene Dx Testing Available
Cerebral Cavernous Malformation 1 (CCM1) KRIT1 Tier 1 Sequencing.
Sequencing of 3 of the 16 coding exons of the CCM1 gene, including the exon containing the location of the 'Common Hispanic' mutation - the identical KRIT1 mutation that is common to many Hispanic families affected with CCMs.
Cerebral Cavernous Malformation 1 (CCM1) KRIT1 Tier 2 Sequencing of the remainder of the CCM1 gene and deletion/duplication analysis of all three CCM genes.
Other CCM1 kindreds harbor other mutations in other exons of the KRIT1 gene. Identification of these other mutations has potential clinical significance for presymptomatic diagnosis of CCM in this population and their families.
Sequencing technology is able to identify a majority of mutations in the genetic code, however it is unable to detect deletion and/or duplication mutations. ExonArray technology, as used by GeneDx, is able to detect deletion or duplication mutations.
Cerebral Cavernous Malformation 2 (CCM2) MGC4607 Mutation Detection by Sequencing.
In families where no KRIT1/CCM1 mutations are shown, CCM2 testing is available.
MGC4607/CCM2 Mutation Test by Sequencing the 10 MGC4607 gene exons
Cerebral Cavernous Malformation 3 (CCM3) PDCD10 Mutation Detection by Sequencing.
A clinical test for the CCM3 gene is available.
PDCD10/CCM3 Mutation Test by Sequencing 7 PDCD10 gene exons
Targeted testing of a relative for specific known sequencing mutation or deletion. In patients where a specific mutation has been demonstrated in a family member, testing will focus on sequencing the exon where the known mutation has been observed.
Attn: Diagnostics Lab
GeneDx
207 Perry Parkway
Gaithersburg, MD20877 USA
Phone: 301-519-2100
FAX: 301-519-2892
www.genedx.com
Page last updated 6.15.10