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Clinically relevant variants identified in thoracic aortic aneurysm patients by research exome sequencing.
- Source :
-
American journal of medical genetics. Part A [Am J Med Genet A] 2016 May; Vol. 170A (5), pp. 1288-94. Date of Electronic Publication: 2016 Feb 07. - Publication Year :
- 2016
-
Abstract
- Thoracic aortic aneurysm (TAA) is a genetically heterogeneous disease involving subclinical and progressive dilation of the thoracic aorta, which can lead to life-threatening complications such as dissection or rupture. Genetic testing is important for risk stratification and identification of at risk family members, and clinically available genetic testing panels have been expanding rapidly. However, when past testing results are normal, there is little evidence to guide decision-making about the indications and timing to pursue additional clinical genetic testing. Results from research based genetic testing can help inform this process. Here we present 10 TAA patients who have a family history of disease and who enrolled in research-based exome testing. Nine of these ten patients had previous clinical genetic testing that did not identify the cause of disease. We sought to determine the number of rare variants in 23 known TAA associated genes identified by research-based exome testing. In total, we found 10 rare variants in six patients. Likely pathogenic variants included a TGFB2 variant in one patient and a SMAD3 variant in another. These variants have been reported previously in individuals with similar phenotypes. Variants of uncertain significance of particular interest included novel variants in MYLK and MFAP5, which were identified in a third patient. In total, clinically reportable rare variants were found in 6/10 (60%) patients, with at least 2/10 (20%) patients having likely pathogenic variants identified. These data indicate that consideration of re-testing is important in TAA patients with previous negative or inconclusive results.<br />Competing Interests: none.<br /> (© 2016 Wiley Periodicals, Inc.)
- Subjects :
- Adolescent
Adult
Aged
Aortic Aneurysm, Thoracic physiopathology
Child
Exome genetics
Female
Genetic Testing
High-Throughput Nucleotide Sequencing
Humans
Intercellular Signaling Peptides and Proteins
Loeys-Dietz Syndrome pathology
Male
Marfan Syndrome pathology
Middle Aged
Mutation
Pedigree
Aortic Aneurysm, Thoracic genetics
Calcium-Binding Proteins genetics
Contractile Proteins genetics
Glycoproteins genetics
Loeys-Dietz Syndrome genetics
Marfan Syndrome genetics
Myosin-Light-Chain Kinase genetics
Smad3 Protein genetics
Transforming Growth Factor beta2 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1552-4833
- Volume :
- 170A
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- American journal of medical genetics. Part A
- Publication Type :
- Academic Journal
- Accession number :
- 26854089
- Full Text :
- https://doi.org/10.1002/ajmg.a.37568