title: Familial thoracic aortic aneurysms and dissections: identification of a novel locus for stable aneurysms with a low risk for progression to aortic dissection.
abstract: BACKGROUND
  Thoracic aortic aneurysms leading to acute aortic dissections are the major diseases that affect the thoracic aorta. Approximately 20% of patients with thoracic aortic aneurysms and dissections (TAAD) have a family history of TAAD, and these patients present younger with more rapidly enlarging aneurysms than patients without a family history of aortic disease.
  
  
  RESULTS
  A large family with multiple members with TAAD inherited in an autosomal-dominant manner was identified. The ascending aortic aneurysms were associated with slow enlargement, a low risk of dissection, and decreased penetrance in women. Genome-wide linkage analysis was performed, and a novel locus on chromosome 12 was identified for the mutant gene causing disease in this family. Of the 12 male members who carry the disease-linked microsatellite haplotype, 9 had ascending aortic aneurysms with an average diameter of 4.7 cm at an average age of 52.4 years (range, 32 to 76 years) at the time of diagnosis; only 1 individual had progressed to acute aortic dissection, and no other members with aortic dissections were identified. Women harboring the disease-linked haplotype did not have thoracic aortic disease, including 1 aged 84 years. Sequencing of 9 genes within the critical interval at the chromosome 12 locus did not identify the mutant gene.
  
  
  CONCLUSIONS
  Mapping a locus for ascending thoracic aortic aneurysms associated with a low risk of aortic dissection supports our hypothesis that genes leading to familial disease can be associated with less-aggressive thoracic aortic disease.
authors.affiliation: University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
authors.forename: Dong-Chuan
authors.initials: DC
authors.lastname: Guo
authors.forename: Ellen S
authors.initials: ES
authors.lastname: Regalado
authors.forename: Charles
authors.initials: C
authors.lastname: Minn
authors.forename: Van
authors.initials: V
authors.lastname: Tran-Fadulu
authors.forename: Joshua
authors.initials: J
authors.lastname: Coney
authors.forename: Jiumei
authors.initials: J
authors.lastname: Cao
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Robert K
authors.initials: RK
authors.lastname: Yu
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Estrera
authors.forename: Hazim J
authors.initials: HJ
authors.lastname: Safi
authors.forename: Sanjay S
authors.initials: SS
authors.lastname: Shete
authors.forename: Dianna M
authors.initials: DM
authors.lastname: Milewicz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000784:Aortic Dissection / Q000150:complications* / Q000235:genetics*; D001011:Aorta / Q000473:pathology*; D017545:Aortic Aneurysm, Thoracic / Q000150:complications* / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D018450:Disease Progression; D005190:Family; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015894:Genome, Human / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012307:Risk Factors; D017422:Sequence Analysis, DNA