title: Increased frequency of FBN1 truncating and splicing variants in Marfan syndrome patients with aortic events.
abstract: OBJECTIVE
  Marfan syndrome is a systemic disorder that typically involves FBN1 mutations and cardiovascular manifestations. We investigated FBN1 genotype-phenotype correlations with aortic events (aortic dissection and prophylactic aortic surgery) in patients with Marfan syndrome.
  
  
  METHODS
  Genotype and phenotype information from probands (n = 179) with an FBN1 pathogenic or likely pathogenic variant were assessed.
  
  
  RESULTS
  A higher frequency of truncating or splicing FBN1 variants was observed in Ghent criteria-positive patients with an aortic event (n = 34) as compared with all other probands (n = 145) without a reported aortic event (79 vs. 39%; P < 0.0001), as well as Ghent criteria-positive probands (n = 54) without an aortic event (79 vs. 48%; P = 0.0039). Most probands with an early aortic event had a truncating or splicing variant (100% (n = 12) and 95% (n = 21) of patients younger than 30 and 40 years old, respectively). Aortic events occurred at a younger median age in patients with truncating/splicing variants (29 years) as compared with those with missense variants (51 years). A trend toward a higher frequency of truncating/splicing variants in patients with aortic dissection (n = 21) versus prophylactic surgery (n = 13) (85.7 vs. 69.3%; not significant) was observed.
  
  
  CONCLUSIONS
  These aortic event- and age-associated findings may have important implications for the management of Marfan syndrome patients with FBN1 truncating and splicing variants.Genet Med 17 3, 177-187.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Linnea M
authors.initials: LM
authors.lastname: Baudhuin
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Katrina E
authors.initials: KE
authors.lastname: Kotzer
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Lagerstedt
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D017398:Alternative Splicing; D001011:Aorta / Q000473:pathology / Q000601:surgery*; D018912:Arabs / Q000235:genetics; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000208:ethnology / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D044465:White People / Q000235:genetics; D055815:Young Adult; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines
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