Dataset Information

Familial aortic disease and a large duplication in chromosome 16p13.1.

ABSTRACT: BACKGROUND AND PURPOSE:A recurrent duplication of chromosome 16p13.1 was associated with aortic dissection as well as with cervical artery dissection. We explore the segregation of this duplication in a family with familial aortic disease. METHODS:Whole exome sequencing (WES) analysis was performed in a patient with a family history of aortic diseases and ischemic stroke due to an aortic dissection extending into both carotid arteries. RESULTS:The index patient, his affected father, and an affected sister of his father carried a large duplication of region 16p13.1, which was also verified by quantitative PCR. The duplication was also found in clinically asymptomatic sister of the index patient. WES did not detect pathogenic variants in a predefined panel of 11 genes associated with aortic disease, but identified rare deleterious variants in 14 genes that cosegregated with the aortic phenotype. CONCLUSIONS:The cosegregation of duplication 16p13.1 with the aortic phenotype in this family suggested a causal relationship between the duplication and aortic disease. Variants in known candidate genes were excluded as disease-causing in this family, but cosegregating variants in other genes might modify the contribution of duplication 16p13.1 on aortic disease.

SUBMITTER: Erhart P

PROVIDER: S-EPMC6014459 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Familial aortic disease and a large duplication in chromosome 16p13.1.

Erhart Philipp P Brandt Tobias T Straub Beate K BK Hausser Ingrid I Hentze Sabine S Böckler Dittmar D Grond-Ginsbach Caspar C

Molecular genetics & genomic medicine 20180214 3

<h4>Background and purpose</h4>A recurrent duplication of chromosome 16p13.1 was associated with aortic dissection as well as with cervical artery dissection. We explore the segregation of this duplication in a family with familial aortic disease.<h4>Methods</h4>Whole exome sequencing (WES) analysis was performed in a patient with a family history of aortic diseases and ischemic stroke due to an aortic dissection extending into both carotid arteries.<h4>Results</h4>The index patient, his affecte ...[more]

PMID: 29441698

Similar Datasets

Project description:BackgroundThoracic aortic disease and bicuspid aortic valve (BAV) likely have a heritable component, but large population-based studies are lacking. This study characterizes familial associations of thoracic aortic disease and BAV, as well as cardiovascular and aortic-specific mortality, among relatives of these individuals in a large-population database.MethodsIn this observational case-control study of the Utah Population Database, we identified probands with a diagnosis of BAV, thoracic aortic aneurysm, or thoracic aortic dissection. Age- and sex-matched controls (10:1 ratio) were identified for each proband. First-degree relatives, second-degree relatives, and first cousins of probands and controls were identified through linked genealogical information. Cox proportional hazard models were used to quantify the familial associations for each diagnosis. We used a competing-risk model to determine the risk of cardiovascular-specific and aortic-specific mortality for relatives of probands.ResultsThe study population included 3 812 588 unique individuals. Familial hazard risk of a concordant diagnosis was elevated in the following populations compared with controls: first-degree relatives of patients with BAV (hazard ratio [HR], 6.88 [95% CI, 5.62-8.43]); first-degree relatives of patients with thoracic aortic aneurysm (HR, 5.09 [95% CI, 3.80-6.82]); and first-degree relatives of patients with thoracic aortic dissection (HR, 4.15 [95% CI, 3.25-5.31]). In addition, the risk of aortic dissection was higher in first-degree relatives of patients with BAV (HR, 3.63 [95% CI, 2.68-4.91]) and in first-degree relatives of patients with thoracic aneurysm (HR, 3.89 [95% CI, 2.93-5.18]) compared with controls. Dissection risk was highest in first-degree relatives of patients who carried a diagnosis of both BAV and aneurysm (HR, 6.13 [95% CI, 2.82-13.33]). First-degree relatives of patients with BAV, thoracic aneurysm, or aortic dissection had a higher risk of aortic-specific mortality (HR, 2.83 [95% CI, 2.44-3.29]) compared with controls.ConclusionsOur results indicate that BAV and thoracic aortic disease carry a significant familial association for concordant disease and aortic dissection. The pattern of familiality is consistent with a genetic cause of disease. Furthermore, we observed higher risk of aortic-specific mortality in relatives of individuals with these diagnoses. This study provides supportive evidence for screening in relatives of patients with BAV, thoracic aneurysm, or dissection.

Dataset Information

Familial aortic disease and a large duplication in chromosome 16p13.1.

Publications

Familial aortic disease and a large duplication in chromosome 16p13.1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets