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A chondrodysplasia family produced by mutations in thediastrophic dysplasia sulfate transporter gene: Genotype/phenotype correlations

✍ Scribed by Superti-Furga, Andrea; Rossi, Antonio; Steinmann, Beat; Gitzelmann, Richard


Publisher
John Wiley and Sons
Year
1996
Tongue
English
Weight
21 KB
Volume
63
Category
Article
ISSN
0148-7299

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✦ Synopsis


Achondrogenesis type 1B (ACG-lB), atelosteogenesis type 2 (A0-2), and diastrophic dysplasia (DTD) are recessively inherited chondrodysplasias of decreasing severity caused by mutations in the diastrophic dysplasia sul- fate transporter (DTDST) gene on chromosome 5. In these conditions, sulfate transport across the cell membrane is impaired which results in insufficient sulfation of cartilage proteoglycans and thus in an abnormally low sulfate content of cartilage. The severity of the phenotype correlates well with the predicted effect of the underlying DTDST mutations: homozygosity or compound heterozygosity for stop codons or transmembrane domain substitutions mostly result in achondrogenesis type lB, while other structural or regulatory mutations usually result in one of the less severe phenotypes. The chondrodysplasias arising at the DTDST locus constitute a bone dysplasia family with recessive inheritance.