Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate-transporter gene (DTDST): evidence for a phenotypic series involving three chondrodysplasias.

Details

Serval ID
serval:BIB_3901B9C2A5E1
Type
Article: article from journal or magazin.
Collection
Publications
Title
Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate-transporter gene (DTDST): evidence for a phenotypic series involving three chondrodysplasias.
Journal
American Journal of Human Genetics
Author(s)
Hästbacka J., Superti-Furga A., Wilcox W.R., Rimoin D.L., Cohn D.H., Lander E.S.
ISSN
0002-9297 (Print)
ISSN-L
0002-9297
Publication state
Published
Issued date
1996
Volume
58
Number
2
Pages
255-262
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. Publication Status: ppublish
Abstract
Atelosteogenesis type II (AO II) is a neonatally lethal chondrodysplasia whose clinical and histological characteristics resemble those of another chondrodysplasia, the much less severe diastrophic dysplasia (DTD). The similarity suggests a shared pathogenesis involving lesions in the same biochemical pathway and perhaps the same gene. DTD is caused by mutations in the recently identified diastrophic dysplasia sulfate-transporter gene (DTDST). Here, we report that AOII patients also have DTDST mutations, which lead to defective uptake of inorganic sulfate and insufficient sulfation of macromolecules by patient mesenchymal cells in vitro. Together with our recent observation that a third even more severe chondrodysplasia, achondrogenesis type IB, is also caused by mutations in DTDST, these results demonstrate a phenotypic series of three chondrodysplasias of increasing severity caused by lesions in a single sulfate-transporter gene. The severity of the phenotype appears to be correlated with the predicted effect of the mutations on the residual activity of the DTDST protein.
Keywords
Anion Transport Proteins, Base Sequence, Biological Transport, Bone and Bones/ultrastructure, Carrier Proteins/genetics, Cloning, Molecular, Fibroblasts, Gene Expression/genetics, Heterozygote, Humans, Infant, Newborn, Membrane Transport Proteins, Molecular Sequence Data, Osteochondrodysplasias/genetics, Osteochondrodysplasias/metabolism, Osteogenesis, Point Mutation/genetics, Proteoglycans/biosynthesis, Proteoglycans/genetics, Sequence Analysis, Sequence Deletion/genetics, Sulfates/metabolism
Pubmed
Web of science
Create date
14/03/2011 16:14
Last modification date
20/08/2019 13:28
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