Hereditary multiple exostoses (EXT)

Mutational studies of familial EXT1 cases and EXT-associated malignancies

Jacqueline T. Hecht, Deborah Hogue, Yang Wang, Susan H Blanton, Michael Wagner, Louise C. Strong, Wendy Raskind, Mark F. Hansen, Dan Wells

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by the formation of cartilage-capped prominences that develop from the growth centers of the long bones. EXT is genetically heterogeneous, with three loci, currently identified on chromosomes 8q24.1, 11p13, and 19q. The EXT1 gene, located on chromosome 8q24.1, has been cloned and is encoded by a 3.4-kb cDNA. Five mutations in the EXT1 gene have been identified-four germ-line mutations, including two unrelated families with the same mutation, and one somatic mutation in a patient with chondrosarcoma. Four of the mutations identified resulted in frameshifts and premature termination codons, while the fifth mutation resulted in a substitution of leucine for arginine. Loss of heterozygosity (LOH) analysis of chondrosarcomas and chondroblastomas revealed multiple LOH events at loci on chromosomes 3q, 8q, 10q, and 19q. One sporadic chondrosarcoma demonstrated LOH for EXT1 and EXT3, while a second underwent LOH for EXT2 and chromosome 10. A third chondrosarcoma underwent LOH for EXT1 and chromosome 3q. These results agree with previous findings that mutations at EXT1 and multiple genetic events that include LOH at other loci may be required for the development of chondrosarcoma.

Original languageEnglish
Pages (from-to)80-86
Number of pages7
JournalAmerican Journal of Human Genetics
Volume60
Issue number1
StatePublished - Jan 1 1997
Externally publishedYes

Fingerprint

Multiple Hereditary Exostoses
Exostoses
Loss of Heterozygosity
Chondrosarcoma
Mutation
Chromosomes
Neoplasms
Chondroblastoma
Chromosomes, Human, Pair 10
Germ-Line Mutation
Nonsense Codon
Leucine
Genes
Cartilage
Arginine
Complementary DNA
Bone and Bones
Growth

ASJC Scopus subject areas

  • Genetics

Cite this

Hereditary multiple exostoses (EXT) : Mutational studies of familial EXT1 cases and EXT-associated malignancies. / Hecht, Jacqueline T.; Hogue, Deborah; Wang, Yang; Blanton, Susan H; Wagner, Michael; Strong, Louise C.; Raskind, Wendy; Hansen, Mark F.; Wells, Dan.

In: American Journal of Human Genetics, Vol. 60, No. 1, 01.01.1997, p. 80-86.

Research output: Contribution to journalArticle

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', American Journal of Human Genetics, vol. 60, no. 1, pp. 80-86.
Hecht, Jacqueline T. ; Hogue, Deborah ; Wang, Yang ; Blanton, Susan H ; Wagner, Michael ; Strong, Louise C. ; Raskind, Wendy ; Hansen, Mark F. ; Wells, Dan. / Hereditary multiple exostoses (EXT) : Mutational studies of familial EXT1 cases and EXT-associated malignancies. In: American Journal of Human Genetics. 1997 ; Vol. 60, No. 1. pp. 80-86.
@article{af6935f33f5e4fbda68046a2df451e7e,
title = "Hereditary multiple exostoses (EXT): Mutational studies of familial EXT1 cases and EXT-associated malignancies",
abstract = "Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by the formation of cartilage-capped prominences that develop from the growth centers of the long bones. EXT is genetically heterogeneous, with three loci, currently identified on chromosomes 8q24.1, 11p13, and 19q. The EXT1 gene, located on chromosome 8q24.1, has been cloned and is encoded by a 3.4-kb cDNA. Five mutations in the EXT1 gene have been identified-four germ-line mutations, including two unrelated families with the same mutation, and one somatic mutation in a patient with chondrosarcoma. Four of the mutations identified resulted in frameshifts and premature termination codons, while the fifth mutation resulted in a substitution of leucine for arginine. Loss of heterozygosity (LOH) analysis of chondrosarcomas and chondroblastomas revealed multiple LOH events at loci on chromosomes 3q, 8q, 10q, and 19q. One sporadic chondrosarcoma demonstrated LOH for EXT1 and EXT3, while a second underwent LOH for EXT2 and chromosome 10. A third chondrosarcoma underwent LOH for EXT1 and chromosome 3q. These results agree with previous findings that mutations at EXT1 and multiple genetic events that include LOH at other loci may be required for the development of chondrosarcoma.",
author = "Hecht, {Jacqueline T.} and Deborah Hogue and Yang Wang and Blanton, {Susan H} and Michael Wagner and Strong, {Louise C.} and Wendy Raskind and Hansen, {Mark F.} and Dan Wells",
year = "1997",
month = "1",
day = "1",
language = "English",
volume = "60",
pages = "80--86",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - Hereditary multiple exostoses (EXT)

T2 - Mutational studies of familial EXT1 cases and EXT-associated malignancies

AU - Hecht, Jacqueline T.

AU - Hogue, Deborah

AU - Wang, Yang

AU - Blanton, Susan H

AU - Wagner, Michael

AU - Strong, Louise C.

AU - Raskind, Wendy

AU - Hansen, Mark F.

AU - Wells, Dan

PY - 1997/1/1

Y1 - 1997/1/1

N2 - Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by the formation of cartilage-capped prominences that develop from the growth centers of the long bones. EXT is genetically heterogeneous, with three loci, currently identified on chromosomes 8q24.1, 11p13, and 19q. The EXT1 gene, located on chromosome 8q24.1, has been cloned and is encoded by a 3.4-kb cDNA. Five mutations in the EXT1 gene have been identified-four germ-line mutations, including two unrelated families with the same mutation, and one somatic mutation in a patient with chondrosarcoma. Four of the mutations identified resulted in frameshifts and premature termination codons, while the fifth mutation resulted in a substitution of leucine for arginine. Loss of heterozygosity (LOH) analysis of chondrosarcomas and chondroblastomas revealed multiple LOH events at loci on chromosomes 3q, 8q, 10q, and 19q. One sporadic chondrosarcoma demonstrated LOH for EXT1 and EXT3, while a second underwent LOH for EXT2 and chromosome 10. A third chondrosarcoma underwent LOH for EXT1 and chromosome 3q. These results agree with previous findings that mutations at EXT1 and multiple genetic events that include LOH at other loci may be required for the development of chondrosarcoma.

AB - Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by the formation of cartilage-capped prominences that develop from the growth centers of the long bones. EXT is genetically heterogeneous, with three loci, currently identified on chromosomes 8q24.1, 11p13, and 19q. The EXT1 gene, located on chromosome 8q24.1, has been cloned and is encoded by a 3.4-kb cDNA. Five mutations in the EXT1 gene have been identified-four germ-line mutations, including two unrelated families with the same mutation, and one somatic mutation in a patient with chondrosarcoma. Four of the mutations identified resulted in frameshifts and premature termination codons, while the fifth mutation resulted in a substitution of leucine for arginine. Loss of heterozygosity (LOH) analysis of chondrosarcomas and chondroblastomas revealed multiple LOH events at loci on chromosomes 3q, 8q, 10q, and 19q. One sporadic chondrosarcoma demonstrated LOH for EXT1 and EXT3, while a second underwent LOH for EXT2 and chromosome 10. A third chondrosarcoma underwent LOH for EXT1 and chromosome 3q. These results agree with previous findings that mutations at EXT1 and multiple genetic events that include LOH at other loci may be required for the development of chondrosarcoma.

UR - http://www.scopus.com/inward/record.url?scp=0031020756&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031020756&partnerID=8YFLogxK

M3 - Article

VL - 60

SP - 80

EP - 86

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 1

ER -