Cerebral Cavernous Malformations via the CCM2 Gene, Exons 2-10 Deletion
- Summary and Pricing
- Clinical Features and Genetics
|Test Code||Test Copy Genes||Price||CPT Code Copy CPT Codes|
The great majority of tests are completed within 18 days.
|CCM2 deletion testing||CCM2 del exon 2-10|
Cerebral cavernous malformations (CCMs) are congenital vascular anomalies of the brain that can cause significant neurological disabilities, including intractable seizures and hemorrhagic stroke. CCMs represent 5-15% of all cerebral vascular malformations and occur in ~0.5% of the general population. CCMs have been reported in infants and children, but the majority of patients present with symptoms between the second and fifth decades. CCMs occur in a sporadic form in which patients usually present with a single lesion and no family history, and a familial form characterized by multiple lesions, and usually a strong family history. A significant fraction of “sporadic” cases with multiple lesions are members of an undiagnosed affected family. Not all patients with CCMs are clinically symptomatic. Symptomatic lesions may often be removed surgically. For additional information, see Zabramski et al. J Neurosurg 80: 422-432, 1994, Morrison and Akers 2011 GeneReviews (http://www.geneclinics.org/), and Angioma Alliance (http://www.angiomaalliance.org/).
Familial Cerebral Cavernous Malformations (CCMs) show autosomal dominant inheritance. Three causative genes for CCMs have been identified: KRIT1 (also called CCM1) encoding a protein that interacts with the Krev-1/rap1a tumor suppressor, CCM2 similar to the KRIT1 binding partner ICAP1α, and PDCD10 (or CCM3) the programmed cell death 10 gene. Almost all causative mutations (in all three genes) are either nonsense, frameshift, splicing or deletion; missense mutations are rare or absent (Denier et al. Ann Neurol 60:550-556, 2006; Plummer et al. Curr Neurol Neurosci Rep 5:391-396, 2005). Liquori et al. (Am J Hum Genet 80:69-75, 2007) reported that deletions in CCM2, especially a 78 kb deletion of exons 2-10, were a frequent cause of CCMs.
This test involves amplification of patient DNA with a specific pair of PCR primers that flank the common CCM2 exon 2-10 deletion. From chromosomes carrying the deletion, an 839 bp PCR product is produced. In normal chromosomes, the PCR primers are ~78 kb apart, and no PCR product is generated. PreventionGenetics also offers Sanger sequencing tests for the full KRIT1, CCM2, and PDCD10 genes (Tests #120-123), a Sanger sequencing test for a common Hispanic Founder mutation (Test #125), and a gene-centric aCGH test for larger copy number variants in all three CCM genes (Test #600).
Indications for Test
Patients with multiple CCMs, or a single CCM and a family history of CCMs. Patients with single lesions and no family history are not likely to give a positive test result.
|Official Gene Symbol||OMIM ID|
|Cerebral Cavernous Malformations Sequencing Panel with CNV Detection|
|Cerebral Cavernous Malformations via CCM2 Gene Sequencing with CNV Detection|
- Genetic Counselor Team - email@example.com
- James L. Weber, PhD - firstname.lastname@example.org
- Akers AL, Johnson E, Steinberg GK, Zabramski JM, Marchuk DA. 2009. Biallelic somatic and germline mutations in cerebral cavernous malformations (CCMs): evidence for a two-hit mechanism of CCM pathogenesis. Hum. Mol. Genet. 18: 919–930. PubMed ID: 19088123
- Denier C, Labauge P, Bergametti F, Marchelli F, Riant F, Arnoult M, Maciazek J, Vicaut E, Brunereau L, Tournier-Lasserve E, Société Française de Neurochirurgie. 2006. Genotype-phenotype correlations in cerebral cavernous malformations patients. Ann. Neurol. 60: 550–556. PubMed ID: 17041941
- Liquori CL, Berg MJ, Squitieri F, Leedom TP, Ptacek L, Johnson EW, Marchuk DA. 2007. Deletions in CCM2 Are a Common Cause of Cerebral Cavernous Malformations. The American Journal of Human Genetics 80: 69–75. PubMed ID: 17160895
- Plummer NW, Zawistowski JS, Marchuk DA. 2005. Genetics of cerebral cavernous malformations. Current neurology and neuroscience reports 5: 391–396. PubMed ID: 16131422
- Zabramski JM, Wascher TM, Spetzler RF, Johnson B, Golfinos J, Drayer BP, Brown B, Rigamonti D, Brown G. 1994. The natural history of familial cavernous malformations: results of an ongoing study. Journal of neurosurgery 80: 422–432. PubMed ID: 8113854
Targeted Deletion Testing via PCR
See methodology section in the supplemental information included in test reports.
myPrevent - Online Ordering
- The test can be added to your online orders in the Summary and Pricing section.
- Once the test has been added log in to myPrevent to fill out an online requisition form.
- A completed requisition form must accompany all specimens.
- Billing information along with specimen and shipping instructions are within the requisition form.
- All testing must be ordered by a qualified healthcare provider.
(Delivery accepted Monday - Saturday)
- Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
- For small babies, we require a minimum of 1 ml of blood.
- Only one blood tube is required for multiple tests.
- Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
- During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
- In cold weather, include an unfrozen ice pack in the shipping container as insulation.
- At room temperature, blood specimen is stable for up to 48 hours.
- If refrigerated, blood specimen is stable for up to one week.
- Label the tube with the patient name, date of birth and/or ID number.
(Delivery accepted Monday - Saturday)
- Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
- For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
- DNA may be shipped at room temperature.
- Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
- We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.
(Delivery preferred Monday - Thursday)
- PreventionGenetics should be notified in advance of arrival of a cell culture.
- Culture and send at least two T25 flasks of confluent cells.
- Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
- Send specimens in insulated, shatterproof container overnight.
- Cell cultures may be shipped at room temperature or refrigerated.
- Label the flasks with the patient name, date of birth, and/or ID number.
- We strongly recommend maintaining a local back-up culture. We do not culture cells.