title: The spectrum of FBN1, TGFβR1, TGFβR2 and ACTA2 variants in 594 individuals with suspected Marfan Syndrome, Loeys-Dietz Syndrome or Thoracic Aortic Aneurysms and Dissections (TAAD).
abstract: BACKGROUND
  In this study, patients suspected of having a clinical diagnosis of Marfan Syndrome (MFS), Loeys-Dietz Syndrome (LDS) and Thoracic Aortic Aneurysms and Dissections (TAAD) were referred for genetic testing and examined for mutations in the FBN1, TGFβR1, TGFβR2 and ACTA2 genes.
  
  
  METHODS
  We examined 594 samples from unrelated individuals and different combinations of genes were sequenced, including one or more of the following: FBN1, TGFβR1, TGFβR2, ACTA2, and, in some cases, FBN1 was analyzed by MLPA to detect large deletions.
  
  
  RESULTS
  A total of 112 patients had a positive result. Of those, 61 had a clinical diagnosis of MFS, eight had LDS, three had TAAD and 40 patients had clinical features with no specific diagnosis provided. A total of 44 patients had an inconclusive result; of these, 12 patients were referred with a clinical diagnosis of MFS, 4 with LDS and 9 with TAAD and 19 had no clinical diagnosis. A total of 89 mutations were novel.
  
  
  CONCLUSIONS
  This study reveals the rate of detection of variants in several genes associated with MFS, LDS and TAAD. The evaluation of patients by individuals with expertise in the field may decrease the likelihood of ordering unnecessary molecular testing. Nevertheless, genetic testing supports the diagnosis of MFS, LDS and TAAD.
authors.affiliation: Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada; Ontario Institute for Cancer Research, Toronto, Ontario, Canada; Laboratory for Molecular Medicine, Partners Healthcare Center for Personalized Genetic Medicine, Cambridge, MA, USA.
authors.forename: Jordan P
authors.initials: JP
authors.lastname: Lerner-Ellis
authors.affiliation: Department of Medicine, University of Toronto, Toronto, ON, Canada. Electronic address: sdubayan@gmail.com.
authors.forename: Saud H
authors.initials: SH
authors.lastname: Aldubayan
authors.affiliation: Laboratory for Molecular Medicine, Partners Healthcare Center for Personalized Genetic Medicine, Cambridge, MA, USA.
authors.forename: Amy Lovelette
authors.initials: AL
authors.lastname: Hernandez
authors.affiliation: Laboratory for Molecular Medicine, Partners Healthcare Center for Personalized Genetic Medicine, Cambridge, MA, USA.
authors.forename: Melissa Allard
authors.initials: MA
authors.lastname: Kelly
authors.affiliation: Boston University, Boston, MA, USA.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Stuenkel
authors.affiliation: Boston University, Boston, MA, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Walsh
authors.affiliation: Laboratory for Molecular Medicine, Partners Healthcare Center for Personalized Genetic Medicine, Cambridge, MA, USA; Departments of Pathology, Massachusetts General Hospital and Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Joshi
mesh_terms: D000199:Actins / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001014:Aortic Aneurysm / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D005820:Genetic Testing; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis* / Q000235:genetics; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D017422:Sequence Analysis, DNA; D055815:Young Adult; D054392:Adipokines
chemical_list: D000199:Actins; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D018125:Receptors, Transforming Growth Factor beta; C541116:ACTA2 protein, human; C000605722:FBN1 protein, human; D054392:Adipokines
keywords: Aortic aneurysms; FBN1; Loeys–Dietz Syndrome; Marfan Syndrome; Thoracic Aortic Aneurysms and Dissections