title: Survival is affected by mutation type and molecular mechanism in vascular Ehlers-Danlos syndrome (EDS type IV).
abstract: OBJECTIVE
  We sought to characterize the natural history of vascular Ehlers-Danlos syndrome in individuals with heterozygous COL3A1 mutations.
  
  
  METHODS
  We reviewed clinical records for details of vascular, bowel, and organ complications in 1,231 individuals (630 index cases and 601 relatives).
  
  
  RESULTS
  Missense and splice-site mutations accounted for more than 90% of the 572 alterations that we had identified in COL3A1. Median survival was 51 years but was influenced by gender (lower in men) and by the type of mutation.
  
  
  CONCLUSIONS
  Although vascular Ehlers-Danlos syndrome appears to be genetically homogeneous, allelic heterogeneity is marked, and the natural history varies with gender and type of mutation in COL3A1. These findings indicate that when counseling families, confirmation of the presence of a COL3A1 mutation and its nature can help evaluate the risks of complications. These data are also important ingredients in both the selection and allocation of individuals to appropriate arms in clinical trials to assess the effects of interventions.
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington, USA.
authors.forename: Melanie G
authors.initials: MG
authors.lastname: Pepin
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington, USA.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schwarze
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Rice
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington, USA.
authors.forename: Mingdong
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington, USA.
authors.forename: Dru
authors.initials: D
authors.lastname: Leistritz
authors.affiliation: 1] Department of Pathology, University of Washington, Seattle, Washington, USA [2] Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Byers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002648:Child; D024061:Collagen Type III / Q000235:genetics*; D004252:DNA Mutational Analysis; D004535:Ehlers-Danlos Syndrome / Q000235:genetics* / Q000401:mortality*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D012326:RNA Splicing; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C439971:COL3A1 protein, human; D024061:Collagen Type III