Fiche publication
Date publication
février 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DOLLE Pascal
Tous les auteurs :
Huckert M, Stoetzel C, Morkmued S, Laugel-Haushalter V, Geoffroy V, Muller J, Clauss F, Prasad MK, Obry F, Raymond JL, Switala M, Alembik Y, Soskin S, Mathieu E, Hemmerle J, Weickert JL, Dabovic B, Rifkin DB, Dheedene A, Boudin E, Caluseriu O, Cholette MC, McLeod R, Antequera R, Gelle MP, Coeuriot JL, Jacquelin LF, Bailleul-Forestier I, Maniere MC, Van Hul W, Bertola D, Dolle P, Verloes A, Mortier G, Dollfus H, Bloch-Zupan A
Lien Pubmed
Résumé
Inherited dental malformations constitute a clinically and genetically heterogeneous group of disorders. Here, we report on four families, three of them consanguineous, with an identical phenotype, characterized by significant short stature with brachyolmia and hypoplastic amelogenesis imperfecta (AI) with almost absent enamel. This phenotype was first described in 1996 by Verloes et al. as an autosomal recessive form of brachyolmia associated with AI. Whole exome sequencing resulted in the identification of recessive hypomorphic mutations including deletion, nonsense and splice mutations, in the LTBP3 gene, which is involved in the TGF-beta signaling pathway. We further investigated gene expression during mouse development and tooth formation. Differentiated ameloblasts synthesizing enamel matrix proteins and odontoblasts expressed the gene. Study of an available knockout mouse model showed that the mutant mice displayed very thin to absent enamel in both incisors and molars, hereby recapitulating the amelogenesis imperfecta phenotype in the human disorder.
Référence
Hum Mol Genet. 2015 Feb 10. pii: ddv053.
