Article: article from journal or magazin.
Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia.
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
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.
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
Web of science
Last modification date