A Compound Heterozygote Harboring Novel and Recurrent DTDST Mutations With Intermediate Phenotype Between Atelosteogenesis Type II and Diastrophic Dysplasia.
Maeda, Koichi 1; Miyamoto, Yoshinari 1; Sawai, Hideaki 2; Karniski, Lawrence P. 3; Nakashima, Eiji 1; Nishimura, Gen 4; Ikegawa, Shiro 1, *
[Article] American Journal Of Medical Genetics -A. 140A(11):1143-1147, June 1, 2006.

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: Diastrophic dysplasia sulfate transporter (DTDST) is a sulfate transporter required for the synthesis of sulfated proteoglycans in the cartilage. Over 30 mutations have been described in the DTDST gene, which result in a continuous clinical spectrum of recessively inherited chondrodysplasias, including, in order of increasing severity, a recessive form of multiple epiphyseal dysplasia (rMED), diastrophic dysplasia (DTD), atelosteogenesis type II (AO-II) and achondrogenesis 1B (ACG-1B). Correlation between disease severity and residual sulfate transport activity has been reported. Here we report a patient with DTDST mutations, whose manifestations fell in a range between AO-II and DTD. The patient was a compound heterozygote for the recurrent c.835C>T (p.R279W) and novel c.1987G>A (p.G663R) mutations. Immunocytochemical analysis in HEK293 cells showed that the p.G663R mutation was localized within the cytoplasm, and not to the cell membrane, suggesting p.G663R is a loss-of-function mutation. Our case supports the previously described correlation between the severity of the phenotype and the putative level of residual transport function. (C) 2006 Wiley-Liss, Inc.

Copyright (C) 2006 John Wiley & Sons, Inc.