Targeted genetic analysis in a large cohort of familial and sporadic cases of aneurysm or dissection of the thoracic aorta
| Autor: | Piyush Gampawar, Jennifer Biggs, Ruwan A. Weerakkody, David A. Parry, Yousef Ibrahim, Bulat A. Ziganshin, Nick Cheshire, Colin Bicknell, Julia Dumfarth, Repository Team, Mark Field, Abdulshakur Abdullah, Timothy J. Aitman, Jana Vandrovcova, John A. Elefteriades, David Ross |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Fibrillin-1 Receptor Transforming Growth Factor-beta Type I Aorta Thoracic VARIANTS 030204 cardiovascular system & hematology Thoracic Aortic Aneurysm/Aortic Dissection (TAAD) 0302 clinical medicine Thoracic aorta Family history Age of Onset Yale Aortic Institute Data and Repository Team Child thoracic aortic aneurysm/aortic dissection Genetics (clinical) Genetics & Heredity Aortic dissection medicine.diagnostic_test High-Throughput Nucleotide Sequencing ASSOCIATION Middle Aged 3. Good health Pedigree Sporadic TAAD Female Life Sciences & Biomedicine TAAD Genetics High-Throughput DNA Sequencing Adult medicine.medical_specialty Adolescent DIAGNOSIS Thoracic aortic aneurysm Article Collagen Type I 03 medical and health sciences Aneurysm medicine.artery Internal medicine Ascending aorta MANAGEMENT medicine Humans Genetic Predisposition to Disease FBN1 Genetic Testing Genetic Association Studies Genetic testing Aged REPAIR 0604 Genetics Science & Technology Aortic Aneurysm Thoracic MUTATIONS business.industry 1103 Clinical Sciences Sequence Analysis DNA FRAMEWORK medicine.disease Collagen Type I alpha 1 Chain 030104 developmental biology Mutation Age of onset business |
| Zdroj: | Weerakkody, R, Ross, D, Parry, D A, Ziganshin, B, Vandrovcova, J, Gampawar, P, Abdullah, A, Biggs, J, Dumfarth, J, Ibrahim, Y, Bicknell, C, Field, M, Elefteriades, J, Cheshire, N & Aitman, T J 2018, ' Targeted genetic analysis in a large cohort of familial and sporadic cases of aneurysm or dissection of the thoracic aorta ', Genetics in Medicine . https://doi.org/10.1038/gim.2018.27 Genetics in medicine : official journal of the American College of Medical Genetics |
| Popis: | PurposeThoracic aortic aneurysm/aortic dissection (TAAD) is a disorder with highly variable age of onset and phenotype. We sought to determine the prevalence of pathogenic variants in TAAD-associated genes in a mixed cohort of sporadic and familial TAAD patients and identify relevant genotype-phenotype relationships.MethodsWe used a targeted polymerase chain reaction and next-generation sequencing-based panel for genetic analysis of 15 TAAD-associated genes in 1,025 unrelated TAAD cases.ResultsWe identified 49 pathogenic or likely pathogenic (P/LP) variants in 47 cases (4.9% of those successfully sequenced). Almost half of the variants were in nonsyndromic cases with no known family history of aortic disease. Twenty-five variants were within FBN1 and two patients were found to harbor two P/LP variants. Presence of a related syndrome, younger age at presentation, family history of aortic disease, and involvement of the ascending aorta increased the risk of carrying a P/LP variant.ConclusionGiven the poor prognosis of TAAD that is undiagnosed prior to acute rupture or dissection, genetic analysis of both familial and sporadic cases of TAAD will lead to new diagnoses, more informed management, and possibly reduced mortality through earlier, preclinical diagnosis in genetically determined cases and their family members.Genetics in Medicine advance online publication, 15 March 2018; doi:10.1038/gim.2018.27. |
| Databáze: | OpenAIRE |
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