title: A novel SMAD3 mutation caused multiple aneurysms in a patient without osteoarthritis symptoms.
abstract: Heterozygous mutations in the SMAD3 gene were recently described as the cause of a form of non-syndromic familial aortic thoracic aneurysm and dissection (FTAAD) transmitted as an autosomal dominant disorder and often associated with early-onset osteoarthritis. This new clinical entity, called aneurysms-osteoarthritis syndrome (AOS) or Loeys-Dietz syndrome 3 (LDS3), is characterized by aggressive arterial damages such as aneurysms, dissections and tortuosity throughout the arterial tree. We report, here, the case of a 45 year-old man presenting multiple visceral arteries and abdominal aortic aneurysms but without dissection of the thoracic aorta and without any sign of osteoarthritis. Exome-sequencing revealed a new frameshift heterozygous c.455delC (p.Pro152Hisfs*34) mutation in the SMAD3 gene. This deletion is located in the exon 3 coding for the linker region of the protein and causes a premature stop codon at positions 556-558 in the exon 4. The same mutation was found in the proband's mother and sister who had open surgery for abdominal aortic aneurysm and in one of his children who was 5 year-old and did not present aneurysm yet.
authors.affiliation: Surgical Research Center, GIGA-R, Belgium; Department of Cardiovascular and Thoracic Surgery, University Hospital of Liège, Belgium. Electronic address: a.courtois@ulg.ac.be.
authors.forename: Audrey
authors.initials: A
authors.lastname: Courtois
authors.affiliation: Genomics Platform, GIGA, Belgium.
authors.forename: Wouter
authors.initials: W
authors.lastname: Coppieters
authors.affiliation: Laboratory of Human Genetics, GIGA-R, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Bours
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, University Hospital of Liège, Belgium.
authors.forename: Jean-Olivier
authors.initials: JO
authors.lastname: Defraigne
authors.affiliation: Laboratory of Connective Tissues Biology, GIGA-R, University of Liège, Sart Tilman, Belgium.
authors.forename: Alain
authors.initials: A
authors.lastname: Colige
authors.affiliation: Surgical Research Center, GIGA-R, Belgium; Department of Cardiovascular and Thoracic Surgery, University Hospital of Liège, Belgium.
authors.forename: Natzi
authors.initials: N
authors.lastname: Sakalihasan
mesh_terms: D000783:Aneurysm / Q000235:genetics*; D000784:Aortic Dissection / Q000235:genetics; D017545:Aortic Aneurysm, Thoracic / Q000235:genetics; D059472:Exome; D005091:Exons; D005192:Family Health; D005260:Female; D016368:Frameshift Mutation; D006579:Heterozygote; D006801:Humans; D055947:Loeys-Dietz Syndrome / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010003:Osteoarthritis / Q000235:genetics*; D010641:Phenotype; D051900:Smad3 Protein / Q000235:genetics*
chemical_list: C497790:SMAD3 protein, human; D051900:Smad3 Protein
keywords: Aneurysms-osteoarthritis syndrome; Aortic aneurysm; Exome sequencing; LDS3; Smad3; TGFβ pathway