Abstract
Achondrogenesis type IB (ACG-IB) is a recessively inherited chondrodysplasia characterized by extremely poor skeletal development and perinatal death1–6. A defect in sulphate metabolism leading to reduced sulphation of proteoglycans has been reported in one case7. The gene for diastrophic dysplasia (DID), a milder chondrodysplasia, was recently shown to encode a sulphate transporter (DTDST)8. We set out to test whether mutations in DTDST might be the cause of ACG-IB using cell cultures, cartilage samples and DMA from six patients. We found that ACGIB cartilage contains less sulphate than control cartilage, and that a sulphation defect is present in all ACG-IB cells and is caused by impaired sulphate uptake. Seven DTDST mutations accounting for all twelve chromosomes were identified in six ACG-IB patients. Thus, ACG-IB and DTD are allelic disorders. While DTD is associated with reduced DTDST expression, ACG-IB is produced by homozy-gosity or compound heterozygos-ity for structural mutations predicting little or no residual activity of the sulphate transporter and represents the null phenotype of DTDST.
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Superti-Furga, A., Hästbacka, J., Wilcox, W. et al. Achondrogenesis type IB is caused by mutations in the diastrophic dysplasia sulphate transporter gene. Nat Genet 12, 100–102 (1996). https://doi.org/10.1038/ng0196-100
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DOI: https://doi.org/10.1038/ng0196-100
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