Pathogenic FBN1 variants in familial thoracic aortic aneurysms and dissections.

TitlePathogenic FBN1 variants in familial thoracic aortic aneurysms and dissections.
Publication TypeJournal Article
Year of Publication2016
AuthorsRegalado, ES, Guo, DC, Santos-Cortez, RLP, Hostetler, E, Bensend, TA, Pannu, H, Estrera, A, Safi, H, Mitchell, AL, Evans, JP, Leal, SM, Bamshad, M, Shendure, J, Nickerson, DA, Milewicz, DM
Corporate AuthorsUniversity of Washington Center for Mendelian Genomics
JournalClin Genet
Date Published2016 06
KeywordsAdult, Aged, Aneurysm, Dissecting, Aortic Aneurysm, Thoracic, Exome, Family Health, Female, Fibrillin-1, Genetic Predisposition to Disease, Humans, Male, Marfan Syndrome, Middle Aged, Mutation, Pedigree, Sequence Analysis, DNA

Marfan syndrome (MFS) due to mutations in FBN1 is a known cause of thoracic aortic aneurysms and acute aortic dissections (TAAD) associated with pleiotropic manifestations. Genetic predisposition to TAAD can also be inherited in families in the absence of syndromic features, termed familial TAAD (FTAAD), and several causative genes have been identified to date. FBN1 mutations can also be identified in FTAAD families, but the frequency of these mutations has not been established. We performed exome sequencing of 183 FTAAD families and identified pathogenic FBN1 variants in five (2.7%) of these families. We also identified eight additional FBN1 rare variants that could not be unequivocally classified as disease-causing in six families. FBN1 sequencing should be considered in individuals with FTAAD even without significant systemic features of MFS.

Alternate JournalClin. Genet.
PubMed ID26621581
PubMed Central IDPMC4873375
Grant ListU54 HG006493 / HG / NHGRI NIH HHS / United States
UL1 RR024148 / RR / NCRR NIH HHS / United States
UM1 HG006493 / HG / NHGRI NIH HHS / United States
P01 HL110869 / HL / NHLBI NIH HHS / United States
R01 HL109942 / HL / NHLBI NIH HHS / United States