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

Journal Article · Thu Feb 01 04:00:00 EST 1996 · American Journal of Human Genetics

OSTI ID:219855

Haestbacka, J; Lander, E S ^[1]; Superti-Furga, A ^[2]

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1. Massachusetts Inst. of Technology, Cambridge, MA (United States)
2. Univ. of Zurich (Switzerland); and others

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. 24 refs., 6 figs., 1 tab.

• OSTI ID: 219855
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 2 Vol. 58; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
GENE MUTATIONS
GENES
HEREDITARY DISEASES
NEONATES
PHENOTYPE
PROTEINS
SKELETAL DISEASES
STRUCTURE-ACTIVITY RELATIONSHIPS
SULFATES
UPTAKE