A novel SMAD3 mutation caused multiple aneurysms in a patient without osteoarthritis symptoms

作者：Courtois Audrey; Coppieters Wouter; Bours Vincent; Defraigne Jean Olivier; Colige Alain; Sakalihasan Natzi

来源：European Journal of Medical Genetics, 2017, 60(4): 228-231.

DOI：10.1016/j.ejmg.2017.02.001

• Aortic aneurysm
• Aneurysms-osteoarthritis syndrome
• LDS3
• Smad3
• TGF beta pathway
• Exome sequencing

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.

• 出版日期2017-4