Thoracic aortic aneurysms and dissections, Marfan syndrome, and other related disorders are serious genetic conditions that often contribute to sudden cardiac death, so an accurate diagnosis is essential to prevent life-threatening events. TAADNext precisely analyzes 35 genes associated with these disorders, helping you confirm a diagnosis that aids in patient management and treatment options.
for all blood relatives of patients who undergo full single gene sequencing, multigene panel testing or exome sequencing at Ambry Genetics and are found to have a pathogenic or likely pathogenic variant. No-cost testing of blood relatives must be completed within 90 days of the original report date. Whenever possible, more closely related relatives should be tested before more distant relatives.
Order NowKnowing if your patient has a hereditary cardiovascular disorder can help you determine their future cardiovascular disease risks and guide your medical management recommendations. Key benefits include:
Up to 93% of patients with Marfan syndrome have a mutation in the FBN1 gene.1 >95% of patients with EDS type IV have a mutation in the COL3A1 gene.2 30-40% of patients with familial TAAD have a mutation in one of the TAADNext genes (clinical sensitivity).3
The FBN1 and TAADNext tests are designed and validated to be capable of detecting >99% of described mutations in the genes represented on the tests (analytical sensitivity). The clinical sensitivity of the FBN1 and TAADNext tests may vary widely according to the specific clinical and family history.
TAADNext is a comprehensive analysis of 35 genes associated with TAAD and related disorders. Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using a standardized kit and quantified. Sequence enrichment of the targeted coding exons and adjacent intronic nucleotides is carried out by a bait-capture methodology using long biotinylated oligonucleotide probes, and is followed by polymerase chain reaction (PCR) and Next-Generation sequencing. Additional Sanger sequencing is performed for any regions missing or with insufficient read depth coverage for reliable heterozygous variant detection. Potentially homozygous variants, variants in regions complicated by pseudogene interference, and variant calls not satisfying depth of coverage and variant allele frequency quality thresholds are verified by Sanger sequencing. This assay targets all coding domains, and well into the flanking 5’ and 3’ ends of all the introns and untranslated regions. Gross deletion/duplication analysis is performed for all genes (excluding CBS and TNXB exons 32-44) using a custom pipeline based on read-depth from NGS data followed by a confirmatory orthogonal method, as needed. Exon-level resolution may not be achieved for every gene.
1. Korkko J, et al. Sensitivity of conformation sensitive gel electrophoresis in detecting mutations in Marfan syndrome and related conditions. J Med Genet. 2002;39:34–41.
2. Pepin MG and Byers PH. Ehlers-Danlos Syndrome Type IV. 1999 Sep 2 [Updated 2011 May 3]. In: Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014.
3. Milewicz DM and Regalado E. Thoracic Aortic Aneurysms and Aortic Dissections. 2003 Feb 13 Updated 2012 Jan 12. In: Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014.