Abstract
Background: Multiple epiphyseal dysplasia (MED) is one of the common hereditary osteochondrodysplasias. Mutations in diastrophic dysplasia sulfate transporter gene (DTDST) result in recessive MED.
Objective: To investigate the possible gene mutation in a recessive MED patient.
Subjects: A boy with typical clinical features of recessive MED and his parents.
Methods: Clinical and radiological evaluations, DTDST gene sequence analysis, and sulfate uptake assay were performed on the patient and his parents.
Results: The patient showed typical symptoms of recessive MED. The radiological evaluation confirmed dysplasia in multiple epiphysis of the patient, while his parents did not show the similar clinical and radiological features. Gene sequence showed the patient was homozygous of A2092T (T689S) mutation, while his parents were both of heterozygous of the same mutation. No such mutation in DTDST gene was found in 81 normal control individuals. The patient showed reduced sulfate uptake ability in dermal fibroblast compared with his parents and normal controls.
Conclusion: The homozygous A2092T (T689S) mutation could be one of the mutations in the DTDST gene causing MED.
We are grateful to Professor Huang Chen (Department of Genetics, Medicine college of Xi’an Jiaotong University) and Dr. Yang Xudong (Department of Biochemistry and Molecular Biology, Medicine college of Xi’an Jiaotong University) for their valuable advice to this study.
References
1. Superti-Furga A, Neumann L, Riebel T, Eich G, Steinmann B, et al. Recessively inherited multiple epiphyseal dysplasia with normal stature, club foot, and double layered patella caused by a DTDST mutation. J Med Genet 1999;36:621–4.Search in Google Scholar
2. Hastbacka J, de la Chapelle A, Mahtani MM, Clines G, Reeve-Daly MP, et al. The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine-structure linkage disequilibrium mapping. Cell 1994;78:1073–87.10.1016/0092-8674(94)90281-XSearch in Google Scholar
3. Haila S, Hastbacka J, Bohling T, Karjalainen-Lindsberg ML, Kere J, et al. SLC26A2 (diastrophic dysplasia sulfate transporter) is expressed in developing and mature cartilage but also in other tissues and cell types. J Histochem Cytochem 2001;49:973–82.10.1177/002215540104900805Search in Google Scholar
4. Rossi A, Bonaventure J, Delezoide AL, Superti-Furga A, Cetta G. Undersulfation of cartilage proteoglycans ex vivo and increased contribution of amino acid sulfur to sulfation in vitro in McAlister dysplasia/atelosteogenesis type 2. Eur J Biochem/FEBS 1997;248:741–7.10.1111/j.1432-1033.1997.t01-1-00741.xSearch in Google Scholar
5. Wallis GA. Cartilage disorders. The importance of being sulphated. Curr Biol 1995;5:225–7.10.1016/S0960-9822(95)00044-3Search in Google Scholar
6. Superti-Furga A, Hastbacka J, Wilcox WR, Cohn DH, van der Harten HJ, et al. Achondrogenesis type IB is caused by mutations in the diastrophic dysplasia sulphate transporter gene. Nat Genet 1996;12:100–2.10.1038/ng0196-100Search in Google Scholar
7. Rossi A, van der Harten HJ, Beemer FA, Kleijer WJ, Gitzelmann R, et al. Phenotypic and genotypic overlap between atelosteogenesis type 2 and diastrophic dysplasia. Hum Genet 1996;98:657–61.10.1007/s004390050279Search in Google Scholar
8. Unger S, Bonafe L, Superti-Furga, A. Multiple epiphyseal dysplasia: clinical and radiographic features, differential diagnosis and molecular basis. Best Pract Res Clin Rheumatol 2008;22:19–32.10.1016/j.berh.2007.11.009Search in Google Scholar
9. Grayeli AB, Escoubet B, Bichara M, Julien N, Silve C, et al. Increased activity of the diastrophic dysplasia sulfate transporter in otosclerosis and its inhibition by sodium fluoride. Otol Neurotol 2003;24:854–62.10.1097/00129492-200311000-00005Search in Google Scholar
10. Imauchi Y, Lombes M, Laine P, Sterkers O, Ferrary E, et al. Glucocorticoids inhibit diastrophic dysplasia sulfate transporter activity in otosclerosis by interleukin-6. Laryngoscope 2006;116:1647–50.10.1097/01.mlg.0000231733.02481.59Search in Google Scholar
11. Cai G, Nakayama M, Hiraki Y, Ozono K. Mutational analysis of the DTDST gene in a fetus with achondrogenesis type 1B. Am J Med Genet 1998;78:58–60.10.1002/(SICI)1096-8628(19980616)78:1<58::AID-AJMG12>3.0.CO;2-NSearch in Google Scholar
12. Rouached H, Berthomieu P, El Kassis E, Cathala N, Catherinot V, et al. Structural and functional analysis of the C-terminal STAS (sulfate transporter and anti-sigma antagonist) domain of the Arabidopsis thaliana sulfate transporter SULTR1.2. J Biol Chem 2005;280:15976–83.10.1074/jbc.M501635200Search in Google Scholar
13. Rossi A, Kaitila I, Wilcox WR, Rimoin DL, Steinmann B, et al. Proteoglycan sulfation in cartilage and cell cultures from patients with sulfate transporter chondrodysplasias: relationship to clinical severity and indications on the role of intracellular sulfate production. Matrix Biol 1998;17:361–69.10.1016/S0945-053X(98)90088-9Search in Google Scholar
14. Forlino A, Piazza R, Tiveron C, Della Torre S, Tatangelo L, et al. A diastrophic dysplasia sulfate transporter (SLC26A2) mutant mouse: morphological and biochemical characterization of the resulting chondrodysplasia phenotype. Hum Mol Genet 2005;14:859–71.10.1093/hmg/ddi079Search in Google Scholar PubMed
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