title: Risk of dissection in thoracic aneurysms associated with mutations of smooth muscle alpha-actin 2 (ACTA2).
abstract: OBJECTIVE
  To evaluate the prevalence and phenotype of smooth muscle alpha-actin (ACTA2) mutations in non-syndromic thoracic aortic aneurysms and dissections (TAAD).
  
  
  METHODS
  Observational study of ACTA2 mutations in TAAD.
  
  
  METHODS
  Centre for Inherited Cardiovascular Diseases.
  
  
  METHODS
  A consecutive series of 100 patients with TAAD. Exclusion criteria included genetically confirmed Marfan syndrome, Loeys-Dietz type 2, familial bicuspid aortic valve and Ehlers-Danlos type IV syndromes.
  
  
  METHODS
  Multidisciplinary clinical and imaging evaluation, genetic counselling and testing of ACTA2, and family screening.
  
  
  METHODS
  Prevalence of ACTA2 mutations and corresponding phenotypes.
  
  
  RESULTS
  TAAD was familial in 43 cases and sporadic in 57 cases. Five mutations in the familial TAAD group (12%) were identified that were absent in controls. The known p.Arg149Cys and the novel p.Asp82Glu, p.Glu243Lys and p.Val45Leu mutations affected evolutionarily conserved residues. The IVS4+1G>A mutation was novel. Of 14 affected relatives, 13 were carriers of the mutation identified in the corresponding proband while one deceased relative had no genetic test. Type A dissection was the first manifestation of aortic aneurysm in four probands and occurred unexpectedly in five relatives. The aortic aneurysm was age dependent and absent in mutated children. Of nine patients who had acute dissection, five died following surgery. At dissection, the size of the aortic aneurysm ranged from 40 mm to 95 mm. Extravascular, ocular, skeletal, nervous and pulmonary traits were variably associated with TAAD, with iris flocculi being most common.
  
  
  CONCLUSIONS
  Timely diagnosis of TAAD in the probands, genetic counselling and family screening identify predisposed relatives and prevent catastrophic aortic dissections.
authors.affiliation: Centre for Inherited Cardiovascular Diseases, IRCCS Fondazione Policlinico San Matteo, Piazzale Golgi 19, Pavia 27100, Italy. e.arbustini@smatteo.pv.it
authors.forename: Eliana
authors.initials: E
authors.lastname: Disabella
authors.forename: Maurizia
authors.initials: M
authors.lastname: Grasso
authors.forename: Fabiana Isabella
authors.initials: FI
authors.lastname: Gambarin
authors.forename: Nupoor
authors.initials: N
authors.lastname: Narula
authors.forename: Roberto
authors.initials: R
authors.lastname: Dore
authors.forename: Valentina
authors.initials: V
authors.lastname: Favalli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Serio
authors.forename: Elena
authors.initials: E
authors.lastname: Antoniazzi
authors.forename: Mario
authors.initials: M
authors.lastname: Mosconi
authors.forename: Michele
authors.initials: M
authors.lastname: Pasotti
authors.forename: Attilio
authors.initials: A
authors.lastname: Odero
authors.forename: Eloisa
authors.initials: E
authors.lastname: Arbustini
mesh_terms: D000199:Actins / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000784:Aortic Dissection / Q000235:genetics*; D017545:Aortic Aneurysm, Thoracic / Q000235:genetics*; D001021:Aortic Valve / Q000002:abnormalities; D002648:Child; D005260:Female; D005819:Genetic Markers; D006801:Humans; D055947:Loeys-Dietz Syndrome / Q000235:genetics; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012307:Risk Factors
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D005819:Genetic Markers