title: Routine Genetic Testing for Thoracic Aortic Aneurysm and Dissection in a Clinical Setting.
abstract: BACKGROUND
  Hereditary factors play an important etiologic role in thoracic aortic aneurysm and dissection (TAAD), with a number of genes proven to predispose to this condition. We initiated a clinical program for routine genetic testing of individuals for TAAD by whole exome sequencing (WES). Here we present our initial results.
  
  
  METHODS
  The WES was performed in 102 patients (mean age 56.8 years; range 13 to 83; 70 males [68.6%]) with TAAD. The following 21-gene panel was tested by WES: ACTA2, ADAMTS10, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, ELN, FBLN4, FLNA, FBN1, FBN2, MYH11, MYLK, NOTCH1, PRKG1, SLC2A10, SMAD3, TGFB2, TGFBR1, TGFBR2.
  
  
  RESULTS
  Seventy-four patients (72.5%) had no medically important genetic alterations. Four patients (3.9%) had a deleterious mutation identified in the FBN1, COL5A1, MYLK, and FLNA genes. Twenty-two (21.6%) previously unreported suspicious variants of unknown significance were identified in 1 or more of the following genes: FBN1 (n = 5); MYH11 (n = 4); ACTA2 (n = 2); COL1A1 (n = 2); TGFBR1 (n = 2); COL3A1 (n = 1); COL5A1 (n = 1); COL5A2 (n = 1); FLNA (n = 1); NOTCH1 (n = 1); PRKG1 (n = 1); and TGFBR3 (n = 1). Identified mutations had implications for clinical management.
  
  
  CONCLUSIONS
  Routine genetic screening of patients with TAAD provides information that enables genetically personalized care and permits identification of novel mutations responsible for aortic pathology. Analysis of large data sets of variants of unknown significance that include associated clinical features will help define the mutational spectrum of known genes underlying this phenotype and potential identify new candidate loci.
authors.affiliation: Aortic Institute at Yale-New Haven, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Bulat A
authors.initials: BA
authors.lastname: Ziganshin
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Allison E
authors.initials: AE
authors.lastname: Bailey
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Celinez
authors.initials: C
authors.lastname: Coons
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Daniel
authors.initials: D
authors.lastname: Dykas
authors.affiliation: Aortic Institute at Yale-New Haven, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Paris
authors.initials: P
authors.lastname: Charilaou
authors.affiliation: Aortic Institute at Yale-New Haven, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Lokman H
authors.initials: LH
authors.lastname: Tanriverdi
authors.affiliation: Aortic Institute at Yale-New Haven, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Lucy
authors.initials: L
authors.lastname: Liu
authors.affiliation: Aortic Institute at Yale-New Haven, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Maryann
authors.initials: M
authors.lastname: Tranquilli
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Allen E
authors.initials: AE
authors.lastname: Bale
authors.affiliation: Aortic Institute at Yale-New Haven, Yale University School of Medicine, New Haven, Connecticut. Electronic address: john.elefteriades@yale.edu.
authors.forename: John A
authors.initials: JA
authors.lastname: Elefteriades
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000784:Aortic Dissection / Q000175:diagnosis* / Q000235:genetics; D017545:Aortic Aneurysm, Thoracic / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005820:Genetic Testing / Q000379:methods*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012189:Retrospective Studies; D055815:Young Adult