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A compound heterozygote harboring novel and recurrent DTDST mutations with intermediate phenotype between atelosteogenesis type II and diastrophic dysplasia
Author(s) -
Maeda Koichi,
Miyamoto Yoshinari,
Sawai Hideaki,
Karniski Lawrence P.,
Nakashima Eiji,
Nishimura Gen,
Ikegawa Shiro
Publication year - 2006
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.31225
Subject(s) - compound heterozygosity , mutation , phenotype , heterozygote advantage , microbiology and biotechnology , dysplasia , genetics , biology , gene , genotype
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. © 2006 Wiley‐Liss, Inc.