title: Mutations in TGFBR2 gene cause spontaneous cervical artery dissection.
abstract: Mutations in the genes encoding transforming growth factor β receptors 1 and 2 (TGFBR1 and TGFBR2) have recently been associated with hereditary connective tissue disorders with widespread vascular involvement, including arterial dissection. To determine whether mutations in these genes cause spontaneous cervical artery dissection (sCAD), all coding exons of TGFBR1 and TGFBR2 were sequenced in 56 consecutive patients with sCAD. Novel TGFBR2 disease causing mutations were found in two patients. The two mutations were the pK327R substitution affecting the kinase domain of TGFBR2 and the pC138R substitution falling in the extracellular domain of the protein, involved in TGFβ binding and signalling. No TGFBR1 mutation was found. The findings indicate that TGFBR2 gene mutations are responsible for sCAD in 3.6% (95% CI 0.0 to 8.4) of cases, have implications in understanding the role of TGFβ signalling in the pathogenesis of sCAD and emphasise the importance of considering molecular characterisation of the TGFBR2 gene in these patients, regardless of the presence of clinical features suggestive of hereditary connective tissue disorders.
authors.affiliation: Dipartimento di Scienze Mediche e Chirurgiche, Clinica Neurologica, Università degli Studi di Brescia, P le Spedali Civili, 1, 25100 Brescia, Italia. ale_pezzini@hotmail.com
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pezzini
authors.forename: Bruno
authors.initials: B
authors.lastname: Drera
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Del Zotto
authors.forename: Marco
authors.initials: M
authors.lastname: Ritelli
authors.forename: Monica
authors.initials: M
authors.lastname: Carletti
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Tomelleri
authors.forename: Paolo
authors.initials: P
authors.lastname: Bovi
authors.forename: Alessia
authors.initials: A
authors.lastname: Giossi
authors.forename: Irene
authors.initials: I
authors.lastname: Volonghi
authors.forename: Paolo
authors.initials: P
authors.lastname: Costa
authors.forename: Mauro
authors.initials: M
authors.lastname: Magoni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
authors.forename: Sergio
authors.initials: S
authors.lastname: Barlati
authors.forename: Marina
authors.initials: M
authors.lastname: Colombi
mesh_terms: D000328:Adult; D000784:Aortic Dissection / Q000235:genetics*; D017545:Aortic Aneurysm, Thoracic / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625841:TGFBR1 protein, human