title: Familial thoracic aortic aneurysm/dissection with patent ductus arteriosus: genetic arguments for a particular pathophysiological entity.
abstract: Thoracic aortic aneurysm and aortic dissection (TAA and AD) are an important cause of sudden death. Familial cases could account for 20% of all cases. A genetic heterogeneity with two identified genes (FBN1 and COL3A1) and three loci (3p24-25 or MFS2/TAAD2, 5q13-q14 and 11q23.2-24) has been shown previously. Study of a single family composed of 179 members with an abnormally high occurrence of TAA/AD disease. A total of 40 subjects from three generations were investigated. In addition to five cases of stroke and three cases of sudden death, there were four cases of AD and four cases of TAA in adults. In all, 11 cases of patent ductus arteriosus (PDA) were observed, two of which were associated with TAA and one with AD. Segregation analysis showed that the distribution of these vascular abnormalities was more likely compatible with a single genetic defect with an autosomal dominant pattern of inheritance. There were no clinical signs of Marfan, Elhers-Danlos vascular type or Char syndromes. Genetic linkage analysis was performed for seven genes or loci implicated in familial TAA/AD disease (COL3A1, FBN1, 3p24-25 or MFS2/TAAD2, 5q13-q14 and 11q23.2-q24), Char syndrome (TFAP2B) or autosomal recessive PDA (12q24). Using different genetic models, linkage with these seven loci was excluded. Familial TAA/AD with PDA is likely to be a particular heritable vascular disorder, with an as yet undiscovered Mendelian genetic basis.
authors.affiliation: INSERM U36, Collège de France, and Département de Génétique, Hôpital Européen Georges Pompidou, Paris, France. pkhauvankien@chu-besançon.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Khau Van Kien
authors.forename: Jean-Eric
authors.initials: JE
authors.lastname: Wolf
authors.forename: Flavie
authors.initials: F
authors.lastname: Mathieu
authors.forename: Limin
authors.initials: L
authors.lastname: Zhu
authors.forename: Nicolas
authors.initials: N
authors.lastname: Salve
authors.forename: Alain
authors.initials: A
authors.lastname: Lalande
authors.forename: Caroline
authors.initials: C
authors.lastname: Bonnet
authors.forename: Gaëtan
authors.initials: G
authors.lastname: Lesca
authors.forename: Henri
authors.initials: H
authors.lastname: Plauchu
authors.forename: Arnaud
authors.initials: A
authors.lastname: Dellinger
authors.forename: Annie
authors.initials: A
authors.lastname: Nivelon-Chevallier
authors.forename: François
authors.initials: F
authors.lastname: Brunotte
authors.forename: Xavier
authors.initials: X
authors.lastname: Jeunemaitre
mesh_terms: D000784:Aortic Dissection / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D017545:Aortic Aneurysm, Thoracic / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D003645:Death, Sudden / Q000209:etiology; D004374:Ductus Arteriosus, Patent / Q000150:complications / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D005602:France; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree; D020521:Stroke / Q000150:complications