title: A compound heterozygote harboring novel and recurrent DTDST mutations with intermediate phenotype between atelosteogenesis type II and diastrophic dysplasia.
abstract: 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.
authors.affiliation: Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, Shirokanedai, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Maeda
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Hideaki
authors.initials: H
authors.lastname: Sawai
authors.forename: Lawrence P
authors.initials: LP
authors.lastname: Karniski
authors.forename: Eiji
authors.initials: E
authors.lastname: Nakashima
authors.forename: Gen
authors.initials: G
authors.lastname: Nishimura
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000025:Abortion, Eugenic; D000595:Amino Acid Sequence; D027321:Anion Transport Proteins; D001483:Base Sequence; D002460:Cell Line; D004252:DNA Mutational Analysis; D005260:Female; D005315:Fetal Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005865:Gestational Age; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D026901:Membrane Transport Proteins / Q000032:analysis / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010009:Osteochondrodysplasias / Q000473:pathology*; D010641:Phenotype; D011247:Pregnancy; D017386:Sequence Homology, Amino Acid; D000076988:Sulfate Transporters; D016216:Ultrasonography, Prenatal
chemical_list: D027321:Anion Transport Proteins; D026901:Membrane Transport Proteins; C089651:SLC26A2 protein, human; D000076988:Sulfate Transporters