title: Identification of a chromosome 11q23.2-q24 locus for familial aortic aneurysm disease, a genetically heterogeneous disorder.
abstract: BACKGROUND
  Aortic aneurysms cause significant mortality, and >20% relate to hereditary disorders. Familial aortic aneurysm (FAA) has been described in such conditions as the Marfan and Ehlers-Danlos type IV syndromes, due to defects in the fibrillin-1 and type III procollagen genes, respectively. Other gene defects that cause isolated aneurysms, however, have not thus far been described.
  
  
  RESULTS
  We studied 3 families affected by FAA. No family met the diagnostic criteria for either Marfan or Ehlers-Danlos syndrome. Echocardiography defined involvement of both the thoracic and abdominal aorta. In family ANA, candidate gene analysis excluded linkage to loci associated with aneurysm formation, including fibrillin-1, fibrillin-2, and type III procollagen, and chromosome 3p24.2-p25. Genome-wide linkage analysis identified a 2.3-cM FAA locus (FAA1) on chromosome 11q23.3-q24 with a maximum multipoint logarithm of the odds score of 4.4. In family ANB, FAA was linked to fibrillin-1. In family ANF, however, FAA was not linked to any locus previously associated with aneurysm formation, including fibrillin-1 and FAA1.
  
  
  CONCLUSIONS
  FAA disease is genetically heterogeneous. We have identified a novel FAA locus at chromosome 11q23.3-q24, a critical step toward elucidating 1 gene defect responsible for aortic dilatation. Future characterization of the FAA1 gene will enhance our ability to achieve presymptomatic diagnosis of aortic aneurysms and will define molecular mechanisms to target therapeutics.
authors.affiliation: Division of Cardiology, Department of Medicine, Weill Medical College of Cornell University, The New York Presbyterian Hospital, New York, NY 10021, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Vaughan
authors.forename: M
authors.initials: M
authors.lastname: Casey
authors.forename: J
authors.initials: J
authors.lastname: He
authors.forename: M
authors.initials: M
authors.lastname: Veugelers
authors.forename: K
authors.initials: K
authors.lastname: Henderson
authors.forename: D
authors.initials: D
authors.lastname: Guo
authors.forename: R
authors.initials: R
authors.lastname: Campagna
authors.forename: M J
authors.initials: MJ
authors.lastname: Roman
authors.forename: D M
authors.initials: DM
authors.lastname: Milewicz
authors.forename: R B
authors.initials: RB
authors.lastname: Devereux
authors.forename: C T
authors.initials: CT
authors.lastname: Basson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001014:Aortic Aneurysm / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002871:Chromosome Banding; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005192:Family Health; D005260:Female; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007223:Infant; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010375:Pedigree