title: Novel TGFBR2 and known missense SMAD3 mutations: two case reports of thoracic aortic aneurysms.
abstract: We report the clinical presentation and genetic screening of 2 patients with thoracic aortic aneurysms. A novel TGFBR2 mutation in the 5'untranslated region (c.-59C>T) was identified in a 31-year-old man with a Stanford type A aortic dissection. Bioinformatics tools showed that c.-59C>T variant was predicted to affect exonic splicing enhancer, as validated by quantitative real-time RT-PCR, revealing a sixfold increase of TGFBR2 mRNA in aneurysmal aortic tissue collected during surgery. A previously described missense mutation, p.E239K, in the SMAD3 gene was identified in a 60-year-old man who presented with diffuse vasculopathy. These findings suggest that the features of aneurysmal disease extending beyond the ascending aorta may help to target SMAD3 genetic screening and that alterations in the core splicing machinery can contribute to aneurysmal disease.
authors.affiliation: IFC-CNR Institute of Clinical Physiology, Pisa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Panesi
authors.affiliation: IFC-CNR Institute of Clinical Physiology, Pisa, Italy. Electronic address: ilenia.foffa@ifc.cnr.it.
authors.forename: Ilenia
authors.initials: I
authors.lastname: Foffa
authors.affiliation: IFC-CNR Institute of Clinical Physiology, Pisa, Italy.
authors.forename: Saverio
authors.initials: S
authors.lastname: Sabina
authors.affiliation: IFC-CNR Institute of Clinical Physiology, Pisa, Italy; Fondazione CNR/Regione Toscana G. Monasterio, Massa, Italy.
authors.forename: Lamia
authors.initials: L
authors.lastname: Ait Ali
authors.affiliation: IFC-CNR Institute of Clinical Physiology, Pisa, Italy; Fondazione CNR/Regione Toscana G. Monasterio, Massa, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Andreassi
mesh_terms: D000328:Adult; D017545:Aortic Aneurysm, Thoracic / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D051900:Smad3 Protein / Q000235:genetics*
chemical_list: D018125:Receptors, Transforming Growth Factor beta; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II