NGS Aortic Dysfunction or Dilation and Related Disorders Panel
|Disorder||Thoracic Aortic Aneurism & Dissection (TAAD)
Arterial tortuosity syndrome
Supravalvular aortic stenosis (SVAS)
This panel consists of 20 genes that have been associated with syndromic and non-syndromic forms of thoracic aortic aneurism and dissection (TAAD). Complications from these disorders can occur at any age, and the presentation can be extremely variable. Inheritance is most often autosomal dominant with incomplete penetrance, but some forms of familial TAAD appear to follow an autosomal recessive pattern. Syndromic conditions that include the potential for aortic dysfunction include the following: Marfan syndrome, Loeys-Dietz syndrome, Ehlers-Danlos syndrome, osteogenesis imperfecta, congenital contractural arachnodactyly, Shprintzen-Goldberg syndrome, and arterial tortuosity syndrome. In addition to cardiovascular findings, skeletal manifestations are common, while craniofacial changes may or may not be present. Non-syndromic familial thoracic aortic aneurism exhibits heterogeneity, and not all causative genes have been identified. Medical surveillance and intervention ranging from medication, routine imaging studies, and surgical correction is critical to reduce the incidence of serious or fatal cardiovascular complications.
For patients with a specific suspected disorder, individual gene sequencing should be considered first.
Molecular testing is useful to confirm the diagnosis and to identify the disease causing mutations within a family to allow for carrier testing and prenatal diagnosis.
The current design of the aortic dysfunction or dilation panel covers the coding region for all 20 genes and the flanking intronic sequences. This method allows for analysis of greater than 98% of the targeted sequence for the detection of nucleotide substitutions and small deletions and duplications. Large deletions and duplications will not be detected by this panel. Mutations and variants identified on the panel are confirmed with Sanger sequencing. All novel and apparently pathogenic changes are reported when found within the coding region as well as within 10 basepairs of each intron/exon boundary for each gene. Promoter and 3' untranslated sequences are not included in the current analysis. It should be noted that the current protocol is not specifically designed to detect copy number alterations and single exon deletions may require additional follow-up to determine whether or not they represent technical artifacts.
We recommend further array-based testing to more accurately address the concerns of dosage alterations. The Cytogenetic Laboratory at GGC offers a high resolution whole genome SNP microarray. The GGC Diagnostic Laboratory Directors are available for further consultation regarding the limitations of the NGS and array testing procedures.
The following gene can also be ordered as an individual sequencing test:
These genes are also included in our NGS Connective Tissue Disorders Panel.
Effective January 1, 2017, all NGS panels are performed on an exome backbone with the potential for reflex to whole exome sequencing at a reduced cost. Please contact the laboratory to discuss the requirements for exome sequencing.
|Specimen Requirements||5 to 10 ml of peripheral blood collected in an EDTA (lavender top) Vacutainer tube is preferred. The minimal blood needed for reliable DNA isolation is 3 ml.|
|Transport||The specimen should be kept at room temperature and delivered via overnight shipping. FedEx is preferred. 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.|
|Turnaround time||8-10 weeks|
If the pathogenic mutation(s) are identified in an affected individual using this panel, prenatal diagnosis is available for future pregnancies. Sanger sequencing will be used for prenatal diagnosis when there is a known familial mutation. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.
Insurance billing is available for this test. The Insurance Billing Form is required along with copies of the authorization or letter of agreement from the insurance company.