Heterozygous TGFBR2 mutations in Marfan syndrome.

Abstract : Marfan syndrome is an extracellular matrix disorder with cardinal manifestations in the eye, skeleton and cardiovascular systems associated with defects in the gene encoding fibrillin (FBN1) at 15q21.1 (ref. 1). A second type of the disorder (Marfan syndrome type 2; OMIM 154705) is associated with a second locus, MFS2, at 3p25-p24.2 in a large French family (family MS1). Identification of a 3p24.1 chromosomal breakpoint disrupting the gene encoding TGF-beta receptor 2 (TGFBR2) in a Japanese individual with Marfan syndrome led us to consider TGFBR2 as the gene underlying association with Marfan syndrome at the MSF2 locus. The mutation 1524G-->A in TGFBR2 (causing the synonymous amino acid substitution Q508Q) resulted in abnormal splicing and segregated with MFS2 in family MS1. We identified three other missense mutations in four unrelated probands, which led to loss of function of TGF-beta signaling activity on extracellular matrix formation. These results show that heterozygous mutations in TGFBR2, a putative tumor-suppressor gene implicated in several malignancies, are also associated with inherited connective-tissue disorders.
Type de document :
Article dans une revue
Nature Genetics, Nature Publishing Group, 2004, 36 (8), pp.855-60. 〈10.1038/ng1392〉
Liste complète des métadonnées

Littérature citée [21 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00143367
Contributeur : Gwenaëlle Collod-Beroud <>
Soumis le : mercredi 20 décembre 2017 - 14:43:09
Dernière modification le : lundi 27 août 2018 - 09:44:38

Fichier

 Accès restreint
Fichier visible le : jamais

Connectez-vous pour demander l'accès au fichier

Identifiants

Collections

Citation

Takeshi Mizuguchi, Gwenaëlle Collod-Beroud, Takushi Akiyama, Marianne Abifadel, Naoki Harada, et al.. Heterozygous TGFBR2 mutations in Marfan syndrome.. Nature Genetics, Nature Publishing Group, 2004, 36 (8), pp.855-60. 〈10.1038/ng1392〉. 〈inserm-00143367v2〉

Partager

Métriques

Consultations de la notice

76