Vascular Malformation NGS Panel

Clinical Information

This panel consists of 21 genes that have been associated with circulatory and lymphatic vascular disorders including telangiectasia, lymphedema, and capillary malformations. The presentation of these disorders can be extremely variable. Inheritance is most often autosomal dominant with incomplete penetrance, but some forms of these conditions appear to follow an autosomal recessive pattern. The hereditary hemorrhagic telangiectasia syndromes may include nosebleeds, gastrointestinal bleeds, and potentially life-threatening brain, liver, or lung hemorrhages. Seizures and headaches may also occur although some individuals remain asymptomatic. Lymphedema syndromes show great variability and may improve or worsen with age, be unilateral or bilateral, and may include additional features of cellulitis, hydrocele, and skin or nail changes. Eye abnormalities, hearing loss, and developmental delays may occur in some of these disorders.

Technical Information

This panel is performed by Next Generation Sequencing and covers the coding regions of the listed genes and the flanking intronic sequences. Promoter, 3′ untranslated sequences, and deep intronic sequences are also covered, but only known disease-causing variants in these regions will be reported. Variants identified on the panel are confirmed with Sanger sequencing if they do not meet certain quality thresholds. Large deletions and duplications (CNVs) affecting the genes of the panel can be detected; however, due to defined settings in the analysis software, CNVs smaller than 2-kb may not be identified (for example, some small exonic level copy number changes may not be identified). Low-level mosaicism may not be detected. Please note that certain types of genetic alterations including trinucleotide repeat expansions, methylation abnormalities, and balanced rearrangements (e.g., inversions, reciprocal translocations) may not be detected by the current analysis.

Specimen Requirements

• The preferred sample type is 3-4 ml of peripheral blood collected in an EDTA (purple top) tube. Extracted DNA and saliva are also accepted for this test. Blood and saliva kits are available by request.
• Send approximately 5µg of extracted DNA at a requested concentration of 90-130 ng/µl.
• If saliva is submitted, and the extracted DNA is below quality control, then you will be contacted to submit a blood sample or the panel can be completed on an exome backbone. Saliva samples must be submitted in an approved saliva kit.

Transport Instructions

• The blood specimen should be kept at room temperature and delivered via overnight shipping. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.
• Extracted DNA should be sent at room temperature via overnight delivery.
• Saliva is stable at room temperature and can be delivered via overnight or ground shipping.