Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia.
Details
Serval ID
serval:BIB_E8F9A93DE61A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia.
Journal
Human Genetics
ISSN
1432-1203 (Electronic)
ISSN-L
0340-6717
Publication state
Published
Issued date
2011
Volume
129
Number
5
Pages
497-502
Language
english
Notes
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
Abstract
Sclerosteosis and Van Buchem disease are related recessive sclerosing bone dysplasias caused by alterations in the SOST gene. We tested the hypothesis that craniodiaphyseal dysplasia (CDD) (MIM 122860), an extremely rare sclerosing bone dysplasia resulting facial distortion referred to as "leontiasis ossea", could also be caused by SOST mutations. We discovered mutations c.61G>A (Val21Met) and c.61G>T (Val21Leu) two children with CDD. As these mutations are located in the secretion signal of the SOST gene, we tested their effect on secretion by transfecting the mutant constructs into 293E cells. Intriguingly, these mutations greatly reduced the secretion of SOST. We conclude that CDD, the most severe form of sclerotic bone disease, is part of a spectrum of disease caused by mutations in SOST. Unlike the other SOST-related conditions, sclerosteosis and Van Buchem disease that are inherited as recessive traits seem to be caused by a dominant negative mechanism.
Keywords
Abnormalities, Multiple/genetics, Bone Morphogenetic Proteins/genetics, Child, Craniofacial Abnormalities/genetics, Female, Genetic Markers/genetics, Humans, Male, Mutation, Protein Interaction Domains and Motifs/genetics, Protein Sorting Signals/genetics
Pubmed
Web of science
Create date
14/03/2011 14:36
Last modification date
20/08/2019 17:11
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