Defective EXT1 causes exostoses 1, TRPS2 and CHDS

Stable Identifier
R-HSA-3656253
Type
Pathway
Species
Homo sapiens
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this pathway in the Pathway Browser

Heparan sulfate (HS) is involved in regulating various body functions functions during development, homeostasis and pathology including blood clotting, angiogenesis and metastasis of cancer cells. Exostosin 1 and 2 (EXT1 and 2) glycosyltransferases are required to form HS. They are able to transfer N-acetylglucosamine (GlcNAc) and glucuronate (GlcA) to HS during its synthesis. The functional form of these enzymes appears to be a complex of the two located on the Golgi membrane. Defects in either EXT1 or EXT2 can cause hereditary multiple exostoses 1 (Petersen 1989) and 2 (McGaughran et al. 1995) respectively (MIM:133700 and MIM:133701), autosomal dominant disorders characterized by multiple projections of bone capped by cartilage resulting in deformed legs, forearms and hands. Trichorhinophalangeal syndrome, type II (TRPS2 aka Langer-Giedion syndrome, LGS) is a disorder that combines the clinical features of trichorhinophalangeal syndrome type I (TRPS1, MIM:190350) and multiple exostoses type I, caused by mutations in the TRPS1 and EXT1 genes, respectively (Langer et al. 1984, Ludecke et al. 1995). Defects in EXT1 may also be responsible for chondrosarcoma (CHDS; MIM:215300) (Schajowicz & Bessone 1967, Hecht et al. 1995).

Literature References
PubMed ID Title Journal Year
6015756 Chondrosarcoma in three brothers. A pathological and genetic study

Schajowicz, F, Bessone, JE

J Bone Joint Surg Am 1967
7711731 Molecular dissection of a contiguous gene syndrome: localization of the genes involved in the Langer-Giedion syndrome

L├╝decke, HJ, Wagner, MJ, Nardmann, J, La Pillo, B, Parrish, JE, Willems, PJ, Haan, EA, Frydman, M, Hamers, GJ, Wells, DE

Hum. Mol. Genet. 1995
2783565 Multiple hereditary osteochondromata

Peterson, HA

Clin. Orthop. Relat. Res. 1989
6496574 The tricho-rhino-phalangeal syndrome with exostoses (or Langer-Giedion syndrome): four additional patients without mental retardation and review of the literature

Langer, LO, Krassikoff, N, Laxova, R, Scheer-Williams, M, Lutter, LD, Gorlin, RJ, Jennings, CG, Day, DW

Am. J. Med. Genet. 1984
8558565 WAGR syndrome and multiple exostoses in a patient with del(11)(p11.2p14.2)

McGaughran, JM, Ward, HB, Evans, DG

J. Med. Genet. 1995
7726168 Hereditary multiple exostosis and chondrosarcoma: linkage to chromosome II and loss of heterozygosity for EXT-linked markers on chromosomes II and 8

Hecht, JT, Hogue, D, Strong, LC, Hansen, MF, Blanton, SH, Wagner, M

Am. J. Hum. Genet. 1995
Participants
Participant Of
Disease
Name Identifier Synonyms
hereditary multiple exostoses 206 Osteochondromatosis syndrome (disorder) [Ambiguous], Multiple exostosis syndromes, Multiple congenital exostosis
Authored
Reviewed
Created