title: Pathogenic FBN1 variants in familial thoracic aortic aneurysms and dissections.
abstract: 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.
authors.affiliation: Division of Medical Genetics, Department of Internal Medicine, University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA.
authors.forename: E S
authors.initials: ES
authors.lastname: Regalado
authors.affiliation: Division of Medical Genetics, Department of Internal Medicine, University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Guo
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: R L P
authors.initials: RL
authors.lastname: Santos-Cortez
authors.affiliation: Division of Medical Genetics, Department of Internal Medicine, University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA.
authors.forename: E
authors.initials: E
authors.lastname: Hostetler
authors.affiliation: Division of Medical Genetics, Department of Internal Medicine, University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Bensend
authors.affiliation: Division of Medical Genetics, Department of Internal Medicine, University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA.
authors.forename: H
authors.initials: H
authors.lastname: Pannu
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: A
authors.initials: A
authors.lastname: Estrera
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: H
authors.initials: H
authors.lastname: Safi
authors.affiliation: Department of Genetics and Genome Sciences, University Hospitals of Cleveland, Cleveland, OH, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Mitchell
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Evans
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Leal
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Bamshad
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Shendure
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Nickerson
authors.affiliation: Division of Medical Genetics, Department of Internal Medicine, University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Milewicz
mesh_terms: D000328:Adult; D000368:Aged; D000784:Aortic Dissection / Q000235:genetics* / Q000473:pathology; D017545:Aortic Aneurysm, Thoracic / Q000235:genetics* / Q000473:pathology; D059472:Exome / Q000235:genetics; D005192:Family Health; D005260:Female; D000071838:Fibrillin-1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D017422:Sequence Analysis, DNA / Q000379:methods; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; C000605722:FBN1 protein, human; D054392:Adipokines
keywords: FBN1; Marfan syndrome; familial thoracic aortic aneurysm and dissection