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Mutations in the latent TGF-beta binding protein 3 (LTBP3) gene cause brachyolmia with amelogenesis imperfecta.
- Source :
-
Human molecular genetics [Hum Mol Genet] 2015 Jun 01; Vol. 24 (11), pp. 3038-49. Date of Electronic Publication: 2015 Feb 10. - Publication Year :
- 2015
-
Abstract
- 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 AI phenotype in the human disorder.<br /> (© The Author 2015. Published by Oxford University Press.)
- Subjects :
- Adolescent
Amelogenesis Imperfecta diagnostic imaging
Animals
Base Sequence
Child
Consanguinity
DNA Mutational Analysis
Female
Frameshift Mutation
Genetic Association Studies
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mutation, Missense
Osteochondrodysplasias diagnostic imaging
Pedigree
Radiography
Sequence Deletion
Amelogenesis Imperfecta genetics
Latent TGF-beta Binding Proteins genetics
Osteochondrodysplasias genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2083
- Volume :
- 24
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Human molecular genetics
- Publication Type :
- Academic Journal
- Accession number :
- 25669657
- Full Text :
- https://doi.org/10.1093/hmg/ddv053