Capillary Malformation-Arteriovenous Malformation (EPHB4 and RASA1) Sequencing, and (RASA1) Deletion/Duplication
Detect pathogenic RASA1 and EPHB4 variants. Confirm diagnosis in individuals with findings suggestive of capillary malformation-arteriovenous malformation syndrome types 1 and 2.
Polymerase Chain Reaction/Sequencing/Multiplex Ligation-dependent Probe Amplification
Within 1 month
Lavender (EDTA), Pink (K2EDTA), or Yellow (ACD).
Transport 3 mL whole blood. (Min: 1 mL)
Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months
Background Information for Capillary Malformation-Arteriovenous Malformation (EPHB4 and RASA1) Sequencing and (RASA1) Deletion/Duplication:
Characteristics: Multifocal, randomly distributed, capillary malformations (CM) of the skin that may be associated with a fast-flow lesion (arteriovenous malformations [AVM] or arteriovenous fistula). Fast-flow lesions in the skin, muscle, bone, or central nervous system can cause life-threatening complications such as bleeding, congestive heart failure, or neurological consequences. Capillary malformation-arteriovenous malformation syndrome type 1 (CM-AVM1) is caused by RASA1 pathogenic variants; capillary malformation-arteriovenous malformation syndrome type 2 (CM-AVM2) is caused by EBHB4 pathogenic variants.
Incidence: Estimated at 1 in 20,000 for CM-AVM1 and 1 in 12,000 for CM-AVM2.
Inheritance: Autosomal dominant; approximately one-third of RASA1 pathogenic variants are de novo.
Penetrance: 90-95 percent.
Cause: Pathogenic RASA1 and EPHB4 variants.
Clinical Sensitivity: Not well-established, but at least 65 percent.
Methodology: Bidirectional sequencing of all coding regions and intron-exon boundaries of the EPHB4 and RASA1 genes; Multiplex Ligation-dependent Probe Amplification (MLPA) to detect large RASA1 deletions/duplications.
Analytical Specificity and Sensitivity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region variants and deep intronic variants will not be detected. Large deletions/duplications will not be detected in EPHB4. The breakpoints of large RASA1 deletions/duplications will not be determined.
Compliance Statement C: For human genetic inheritable conditions and mutations. This test was developed and its performance characteristics determined by ARUP Laboratories. The U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Component Test Code*||Component Chart Name||LOINC|
- Capillary Malformation-Arteriovenous Malformation1
- Capillary Malformation-Arteriovenous Malformation2
- CM-AVM type 1
- CM-AVM type 2
- RASA 1 related disorders