Molecular basis of multiple exostoses: Mutations in the EXT1 and EXT2 genes

Human Mutation

Volumn 15, Issue 3, 2000, Pages 220-227

  Wuyts, Wim ^a   Van Hul, Wim ^a  

^a UNIVERSITY OF ANTWERP   (Belgium)

Author keywords

Exostoses; EXT1; EXT2; Hereditary multiple exostoses; Mutation analysis; Mutation spectrum; Tumor suppressor gene

Indexed keywords

FRAMESHIFT MUTATION; GENE MUTATION; HEREDITARY MULTIPLE EXOSTOSIS; HUMAN; MISSENSE MUTATION; NONSENSE MUTATION; PRIORITY JOURNAL; REVIEW; TUMOR SUPPRESSOR GENE;

EXOSTOSES, MULTIPLE HEREDITARY; HUMANS; MUTATION; N-ACETYLGLUCOSAMINYLTRANSFERASES; PROTEINS;

EID: 0034053120     PISSN: 10597794     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1098-1004(200003)15:3<220::AID-HUMU2>3.0.CO;2-K     Document Type: Review

References (46)

1. Ahn J, Lüdecke H, Lindow S, Horton WA, Lee B, Wagner MJ, Horsthemke B, Wells DE. 1995. Cloning of the putative tumour suppressor gene for hereditary multiple exostoses (EXT1). Nat Genet 11:137-143.
2. Bartsch O, Wuyts W, Van Hul W, Hecht JT, Meinecke P, Hogue D, Werner W, Zabel B, Hinkel GK, Powell CM, Shaffer LG, Willems PJ. 1996. Delineation of a contiguous gene syndrome with multiple exostoses, enlarged parietal foramina, craniofacial dysostosis and mental retardation, caused by deletions on the short arm of chromosome 11. Am J Hum Genet 58:734-742.
3. Beilaiche Y, The I, Perrimon N. 1998. Tout-velu is a Drosophila homologue of the putative tumour suppressor EXT-1 and is needed for Hh diffusion. Nature 394:85-88.
4. Blanton SH, Hogue D, Wagner M, Wells D, Young ID, Hecht JT. 1996. Hereditary multiple exostoses: confirmation of linkage to chromosomes 8 and 11. Am J Med Genet 62:150-159.
5. Bovée J, Cleton-Jansen A, Wuyts W, Caethoven G, Taminiau A, Bakker E, Van Hul W, Cornelisse P, Hogendoorn P. 1999. EXT mutation analysis and loss of heterozygosity in sporadic and hereditary osteochondromas and secondary chondrosarcomas. Am J Hum Genet 65:689-698.
6. Bridge JA, Paramjit SB, Anderson JR, Neff JR. 1993. Biologic and clinical significance of cytogenetic and molecular cytogenetic abnormalities in benign and malignant cartilaginous lesions. Cancer Genet Cytogenet 69:79-90.
7. Carey DJ. 1997. Syndecans: multifunctional cell-surface co-receptors. Biochem J 327:1-16.
8. Chiurco AA. 1970. Multiple exostoses of bone with fatal spinal cord compression; report of a case and brief review of the literature. Neurology 20:275-278.
9. Clines GA, Ashley JA, Shah S, Lovett M. 1997. The structure of the human multiple exostoses 2 gene and characterization of homologs in mouse and caenorhabditis elegans. Genome Res 7:359-367.
10. Cook A, Raskind W, Blanton SH, Pauli RM, Gregg RG, Francomano CA, Puffenberger E, Conrad EU, Schmale G, Schellenberg G, Wijsman E, Hecht JT, Wells D, Wagner MJ. 1993. Genetic heterogeneity in families with hereditary multiple exostoses. Am J Hum Genet 53:71-79.
11. Hecht JT, Hogue D, Strong LC, Hansen MF, Blanton SH, Wagner M. 1995. Hereditary multiple exostosis and chondrosarcoma: linkage to chromosome 11 and loss of heterozygozity for EXT-linked markers on chromosomes 11 and 8. Am J Hum Genet 56:1125-1131.
12. Hecht JT, Hogue D, Wang Y, Blanton SH, Wagner M, Strong LC, Raskind W, Hansen MF, Wells D. 1997. Hereditary multiple exostoses (EXT): Mutational studies of familial EXT1 cases and EXT-associated malignancies. Am J Hum Genet 60:80-86.
13. Hennekam RCM. 1991. Hereditary multiple exostoses. J Med Genet 28:262-266.
14. Hogue DA, Clines G, Lovett M, Hansen MF, Hecht JT 1996. Mutational analysis of hereditary multiple exostoses. Am J Hum Genet 59:A263
15. Jaffe HL. 1943. Hereditary multiple exostoses. Arch Pathol 36:335-357.
16. Kitagawa H, Shimakawa H, Sugahara K. 1999. The tumor suppressor EXT-like gene EXTL2 encodes an alpha 1, 4-N-acetylhexosaminyltransferase that transfers N-acetylgalactosamine and N-acetylglucosamine to the common glycosaminoglycan-protein linkage region - the key enzyme for the chain initiation of heparan sulfate. J Biol Chem 274:13933-13937.
17. Langer LO, Krassikoff N, Laxova R, Scheer-Williams M, Lutter LD, Gorlin RJ, Jennings CG. 1984. The trichorhino-phalangeal syndrome with exostoses (or Langer-Giedion syndrome): four additional patients without mental retardation and review of the literature. Am J Med Genet 19:81-111.
18. Le Merrer M, Legeai-Mallet L, Jeannin PM, Horsthemke B, Schinzel A, Plauchu H, Toutain A, Achard F, Munnich A, Maroteaux P. 1994. A gene for hereditary multiple exostoses maps to chromosome 19p. Hum Mol Genet 3:717-722.
19. Legeai-Mallet L, Margaritte-Jeannin P, Lemdani M, Le Merrer M, Plauchu H, Maroteaux P, Munnich A, Clerget-Darpoux F. 1997. An extension of the admixture test for the study of genetic heterogeneity in hereditary multiple exostoses. Hum Genet 99:298-302.
20. Lind T, Tufaro F, McCormick C, Lindahl U, Lidholt K. 1998. The putative tumor suppressors EXT1 and EXT2 are glycosyltranserases required for the biosynthesis of heparan sulfate. J Biol Chem 273:26265-26268.
21. Lohmann DR, Brandt B, Hopping W, Passarge E, Horsthemke B. 1994. Spectrum of small length germline mutations in the RB1 gene. Hum Mol Genet 3:2187-2193.
22. Luckert Wicklund C, Pauli RM, Johnston D, Hecht JT. 1995. Natural history study of hereditary multiple exostoses. Am J Med Genet 55:43-46.
23. Lüdecke HJ, Wagner MJ, Nardmann J, La Pillo B, Parrish JE, Willems PJ, Haan EA, Frydman M, Hamers GJH, Wells DE, Horsthemke B. 1995. Molecular dissection of a contiguous gene syndrome: localization of the genes involved in the Langer-Giedion syndrome. Hum Mol Genet 4:31-36.
24. Lüdecke H-J, Ahn J, Lin X, Hill A, Wagner MJ, Schomburg L, Horsthemke B, Wells DE. 1997. Genomic organization and promotor structure of the human EXT1 gene. Genomics 40:351-354.
25. McCormick C, Leduc Y, Martindale D, Mattison K, Esford LE, Dyer AP, Tufaro F. 1998. The putative tumour suppressor EXT1 alters the expression of cell-surface heparan sulfate. Nat Genet 19:158-161.
26. Mertens F, Rydholm A, Kreicbergs A, Willen H, Jonsson K, Heim S, Mitelman F, Mandahl N. 1994. Loss of chromosome band 8q24 in sporadic osteocartilaginous exostoses. Genes Chromosomes Cancer 9:8-12.
27. Park KJ, Shin KH, Ku JL, Cho TJ, Lee SH, Choi IH, Phillipe C, Monaco AP, Porter DE, Park JG. 1999. Germline mutations in the EXT1 and EXT2 genes in Korean patients with hereditary multiple exostoses. J Hum Genet 44:230-234.
28. Philippe C, Porter DE, Emerton ME, Wells DE, Hamish A, Simpson RW Monaco AP. 1997. Mutation screening of EXT1 and EXT2 genes in patients with hereditary multiple exostoses. Am J Hum Genet 61:520-528.
29. Raskind WH, Conrad EU, Chansky H, Matsushita M. 1995. Loss of heterozygosity in chondrosarcomas for markers linked to hereditary multiple exostoses loci on chromosomes 8 and 11. Am J Hum Genet 56:1132-1139.
30. Raskind WH, Conrad EU, Matsushita M, Wijsman EM, Wells DE, Chapman N, Sandell LJ, Wagner M, Houck J. 1998. Evaluation of locus heterogeneity and EXT1 mutations in 34 families with hereditary multiple exostoses. Hum Mutat 11:231-239.
31. Schmale GA, Conrad EU, Raskind WH. 1994. The natural history of hereditary multiple exostoses. J Bone Joint Surg Am 76:986-992.
32. Shapiro F, Simon S, Glimcher MJ. 1979. Hereditary multiple exostoses. J Bone Joint Surg Am 61:815-824.
33. Solomon L. 1961. Bone growth indiaphyseal aclasis. J Bone Joint Surg Am 43:700-716.
34. Solomon L. 1963. Hereditary multiple exostosis. J Bone Joint Surg Br 45:292-304.
35. Stickens D, Clines G, Burbee D, Ramos P, Thomas S, Hogue D, Hecht JT, Lovett M, Evans GA. 1996. The EXT2 multiple exostoses gene defines a family of putative tumour suppressor genes. Nature Genet 14:25-32.
36. Van Hul W, Wuyts W, Hendrickx J, Speleman F, Wauters J, De Boulle K, Van Roy N, Bossuyt P, Willems PJ. 1998. Identification of a third EXT-like gene (EXTL3) belonging to the EXT gene family. Genomics 47:230-237.
37. Vortkamp A, Lee K, Lanske B, Segre GV Kronenberg HM, Tabin CJ. 1996. Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein. Science 273:613-622.
38. Wise CA, Clines GA, Massa H, Trask BJ, Lovett M. 1997. Identification and localization of the gene for EXTL, a third member of the multiple exostoses gene family. Genome Res 7:10-16.
39. Wolf M, Hemminki A, Kivioja A, Sistonen P, Kaitila I, Ervasti H, Kinnunen J, Karaharju E, Knuutila S. 1998. A novel splice site mutation of the EXT2 gene in a Finnish hereditary multiple exostoses family. Hum Mutat 12:362.
40. Woods A, Couchman JR. 1998. Syndecans: synergistic activators of cell adhesion. Trends Cell Biol 8:189-192.
41. Wu Y, Heutink P, de Vries B, Sandkuijl LA, van den Ouweland AMW, Niermeijer MF, Galjaard H, Reyniers E, Willems PJ, Halley DJJ. 1994. Assignment of a second locus for multiple exostoses to the pericentromeric region of chromosome 11. Hum Mol Genet 3:167-171.
42. Wuyts W, Ramlakhan S, Van Hul W, Hecht JT, van den Ouweland AMW, Raskind W, Hofstede FC, Reyniers E, Wells DE, de Vries B, Conrad EU, Hill A, Zalatayev D, Weissenbach J, Wagner MJ, Bakker E, Halley DJJ, Willems PJ. 1995. Refinement of the multiple exostoses locus (EXT2) to a 3 cM interval on chromosome 11. Am J Hum Genet 57:382-387.
43. Wuyts W, Van Hul W, Wauters J, Nemtsova M, Reyniers E, Van Hul E, De Boulle K, de Vries BBA, Hendrickx J, Herrygers I, Bossuyt P, Balemans W, Fransen E, Vits L, Coucke P, Nowak NJ, Shows TB, Mallet L, van den Ouweland AMW, McGaughran J, Halley DJJ, Willems PJ. 1996. Positional cloning of a gene involved in hereditary multiple exostoses. Hum Mol Genet 5:1547-1557.
44. Wuyts W, Van Hul W, Hendrickx J, Wauters J, Speleman F, De Boulle K, Bossuyt P, Van Agtmael T, Willems PJ. 1997. Identification and characterization of a novel member of the EXT gene family, EXTL2. Eur J Hum Genet 5:382-389.
45. Wuyts W, Van Hul W, De Boulle K, Hendrickx J, Bakker E, Vanhoenacker F, Mollica F, Lüdecke H-J, Sayli B, Pazzaglia UE, Mortier G, Hamel B, Conrad EU, Matsushita M, Raskind W, Willems PJ. 1998. Mutations in the EXT1 and EXT2 genes in hereditary multiple exostoses. Am J Hum Genet 62:346-354.
46. Xu L, Xia J, Jiang H, Zhou J, Li H, Wang D, Pan Q, Long Z, Fan C, Deng HX. 1999. Mutation analysis of hereditary multiple exostoses in the Chinese. Hum Genet 105:45-50.