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UP:P50443 (S26A2_HUMAN)

Friday 5 January 2007

The gene SLC26A2 encodes for a widely distributed sulfate/chloride antiporter of the cell membrane whose function is crucial for the uptake of inorganic sulfate that is needed for proteoglycan sulfation. This sulfate transporter may play a role in endochondral bone formation.


- germline mutations in the SLC26A2 cause a family of recessive chondrodysplasias:

  • achondrogenesis 1B (ACG1B) (MIM.600972)
  • atelosteogenesis 2
  • diastrophic dysplasia
  • recessive multiple epiphyseal dysplasia

- Defects in SLC26A2 are the cause of diastrophic dysplasia (DTD) (MIM.222600). DTD is an autosomal recessive disease characterized by osteochondrodysplasia with clinical features including dwarfism, spinal deformation, and specific joint abnormalities.

- Defects in SLC26A2 are the cause of achondrogenesis type 1B (ACG1B) )MIM:600972). ACG1B is a recessively inherited chondrodysplasia characterized by extremely poor skeletal development and perinatal death.

- Defects in SLC26A2 are the cause of atelosteogenesis type 2 (AO2) (MIM,256050); also known as neonatal osseous dysplasia 1. AO2 is characterized by severely shortened limbs, small chest, scoliosis, club foot of the equinovarus type (talipes equinovarus), abducted thumbs and great toes, and cleft palate. Patients die of respiratory insufficiency shortly after birth because of the collapse of the airways and pulmonary hypoplasia due to the small rib cage.

- Defects in SLC26A2 are the cause of multiple epiphyseal dysplasia type 4 (EDM4) (MIM.226900). EDM is a generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. EDM is broadly categorized into the more severe Fairbank and the milder Ribbing types. EDM4 is a recessively inherited form, characterized by early childhood-onset hip dysplasia and recurrent patella dislocation. Short stature in EDM4 patients is not frequent.

Animnal models

- Homozygous mutant mice were characterized by skeletal dysplasia with chondrocytes of irregular size, delay in the formation of the secondary ossification centre and osteoporosis of long bones. Impaired sulfate uptake was demonstrated in chondrocytes, osteoblasts and fibroblasts, but proteoglycan undersulfation was detected only in cartilage. (17120769)

See also

- osteochondrodysplasias (skeletal dysplasia)
- loss of function mutations
- sulfate transporter


- Autosomal recessive multiple epiphyseal dysplasia with homozygosity for C653S in the DTDST gene: double-layer patella as a reliable sign. Maekitie O., Savarirayan R., Bonafe L., Robertson S., Susic M., Superti-Furga A., Cole W.G. Am. J. Med. Genet. A 122:187-192(2003) [PubMed: 12966518]

- Homozygosity for a novel DTDST mutation in a child with a ’broad bone-platyspondylic’ variant of diastrophic dysplasia. Megarbane A., Haddad F.A., Haddad-Zebouni S., Achram M., Eich G., Le Merrer M., Superti-Furga A. Clin. Genet. 56:71-76(1999) [PubMed: 10466420]

- Achondrogenesis type IB is caused by mutations in the diastrophic dysplasia sulphate transporter gene. Superti-Furga A., Haestbacka J., Wilcox W.R., Cohn D.H., van der Harten H.J., Rossi A., Blau N., Rimoin D.L., Steinmann B., Lander E.S., Gitzelmann R. Nat. Genet. 12:100-102(1996) [PubMed: 8528239]

- Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate-transporter gene (DTDST): evidence for a phenotypic series involving three chondrodysplasias. Haestbacka J., Superti-Furga A., Wilcox W.R., Rimoin D.L., Cohn D.H., Lander E.S. Am. J. Hum. Genet. 58:255-262(1996) [PubMed: 8571951]

- The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine-structure linkage disequilibrium mapping. Haestbacka J., de la Chapelle A., Mahtani M.M., Clines G., Reeve-Daly M.P., Daly M., Hamilton B.A., Kusumi K., Trivedi B., Weaver A., Coloma A., Lovett M., Buckler A., Kaitila I., Lander E.S. Cell 78:1073-1087(1994) [PubMed: 7923357]