Mutation screening of the EXT1 and EXT2 genes in patients with hereditary multiple exostoses.

@article{Philippe1997MutationSO,
  title={Mutation screening of the EXT1 and EXT2 genes in patients with hereditary multiple exostoses.},
  author={C. Philippe and D. Porter and M. Emerton and D. Wells and A. Simpson and A. Monaco},
  journal={American journal of human genetics},
  year={1997},
  volume={61 3},
  pages={
          520-8
        }
}
Hereditary multiple exostoses (HME), the most frequent of all skeletal dysplasias, is an autosomal dominant disorder characterized by the presence of multiple exostoses localized mainly at the end of long bones. HME is genetically heterogeneous, with at least three loci, on 8q24.1 (EXT1), 11p11-p13 (EXT2), and 19p (EXT3). Both the EXT1 and EXT2 genes have been cloned recently and define a new family of potential tumor suppressor genes. This is the first study in which mutation screening has… Expand
Novel EXT1 and EXT2 mutations in hereditary multiple exostoses families of Indian origin.
TLDR
The findings expand the mutation spectrum of EXT1 and EXT2 and highlight the genetic and phenotypic heterogeneity of HME. Expand
Germline mutations in the EXT1 and EXT2 genes in Korean patients with hereditary multiple exostoses
TLDR
A mutational analysis of EXT1 and EXT2 genes in eight unrelated Korean EXT families by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis followed by direct DNA sequencing identified two mutations, which are novel ones. Expand
Mutation frequencies of EXT1 and EXT2 in 43 Japanese families with hereditary multiple exostoses.
TLDR
Results expand the knowledge of the ethnic difference of EXT and the structure-function relationship of the EXT genes by finding all four EXT1 missense mutations occurred in an arginine residue at codon 340 (R340) that is known as a critical site for expression of heparan sulfate glycosaminoglycans, suggesting that the region encompassing the arginin residue may play an important role in the function of theEXT1 protein. Expand
Three novel EXT1 and EXT2 gene mutations in Taiwanese patients with multiple exostoses.
TLDR
Mutation analysis in families with HME allows for genetic counseling and prenatal diagnosis and finds three novel mutations and a known mutation in the EXT1 and EXT2 genes. Expand
Mutations in the EXT1 and EXT2 genes in hereditary multiple exostoses.
TLDR
It is concluded that mutations in either the EXT1 or the EXT2 gene are responsible for the majority of EXT cases, and most of the mutations in EXT1 and EXT2 cause premature termination of the EXT proteins, whereas missense mutations are rare. Expand
Mutation spectrum of EXT1 and EXT2 in the Saudi patients with hereditary multiple exostoses
TLDR
Extended EXT1 and EXT2 mutations contribute significantly to the pathogenesis of HME in the Saudi population and the six novel EXT1 /EXT2 mutations further expands the mutation spectrum of Hme. Expand
Mutation screening of the EXT genes in patients with hereditary multiple exostoses in Taiwan.
TLDR
The results indicate that in familial cases, linkage analysis can prove useful for preimplantation genetic diagnosis, and four new mutations that have not been found in other races are identified. Expand
Mutation screening for the EXT1 and EXT2 genes in Chinese patients with multiple osteochondromas.
TLDR
The findings of this study are useful for extending the mutational spectrum in EXT1 and EXT2 and understanding the genetic basis of MO in Chinese patients. Expand
Novel mutation in the EXT-1 gene in an Iranian family affected with hereditary multiple exostoses.
TLDR
In this first report from Iran, a frame shift mutation (1100-1101 insA) in exon 3 of EXT1 gene in a family being suspicious of HME is identified and an unreported silent mutation in the exon six ofEXT1 gene with uncertain significance is found. Expand
Molecular basis of multiple exostoses: mutations in the EXT1 and EXT2 genes
TLDR
The majority of these mutations are mutations causing loss of function, which is consistent with the presumed tumor suppressor function of the EXT genes. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 32 REFERENCES
Positional cloning of a gene involved in hereditary multiple exostoses.
TLDR
To isolate the EXT2 gene, a contig of yeast artificial chromosomes and P1 clones covering the complete EXT2 candidate region on chromosome 11p11-p12 was constructed and one of the transcribed sequences corresponds to a novel gene with homology to the EXT1 gene, and harbours inactivating mutations in different patients with hereditary multiple exostoses. Expand
Hereditary multiple exostoses (EXT): mutational studies of familial EXT1 cases and EXT-associated malignancies.
TLDR
Detailed loss of heterozygosity (LOH) analysis of chondrosarcomas and chondroblastomas revealed multiple LOH events at loci on chromosomes 3q, 8q, 10q, and 19q, which 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 chondsarcoma. Expand
Identification of novel mutations in the human EXT1 tumor suppressor gene
TLDR
Six mutations in the human EXT1 gene are identified from six unrelated multiple exostoses families segregating for the EXT gene on chromosome 8, and one of the mutations is the same 1-bp deletion in exon 6 that was previously reported in two independent EXT families. Expand
Identification and localization of the gene for EXTL, a third member of the multiple exostoses gene family.
TLDR
A third gene is identified that shows striking sequence similarity to both EXT1 and EXT2 at the nucleotide and amino acid sequence levels, and is therefore a new member of the EXT gene family and is a potential candidate for several disease phenotypes. Expand
Hereditary multiple exostosis and chondrosarcoma: linkage to chromosome II and loss of heterozygosity for EXT-linked markers on chromosomes II and 8.
TLDR
The findings suggest that EXT genes may be tumor-suppressor genes and that the initiation of tumor development may follow a multistep model. Expand
Cloning of the putative tumour suppressor gene for hereditary multiple exostoses (EXT1)
TLDR
Cloned and characterized a cDNA which spans chromosomal breakpoints previously identified in two multiple exostoses patients, and suggests that the 8q24.1–encoded EXT1 gene may have tumour suppressor function. Expand
An extension of the admixture test for the study of genetic heterogeneity in hereditary multiple exostoses
TLDR
The present approach can be generalized to the investigation of genetic heterogeneity in other monogenic diseases, as it simultaneously estimates the location of each disease gene and the proportion of families linked to each locus. Expand
Loss of heterozygosity in chondrosarcomas for markers linked to hereditary multiple exostoses loci on chromosomes 8 and 11.
TLDR
The hypothesis that genes on 8q and the pericentromeric region of 11 have tumor-suppressor function and play a role in the development of chondrosarcomas is supported. Expand
The EXT2 multiple exostoses gene defines a family of putative tumour suppressor genes
TLDR
This gene shows striking sequence similarity to the EXT1 gene, and a four base deletion segregating with the phenotype is identified, defining a new multigene family of proteins with potential tumour suppressor activity. Expand
Refinement of the multiple exostoses locus (EXT2) to a 3-cM interval on chromosome 11.
TLDR
Linkage analysis in seven extended EXT families, all linked to the EXT2 locus, refined the localization of theEXT2 gene to a 3-cM region flanked by D11S1355 and D 11S1361/D11S554, which implies that the SPACE2 gene is located at the short arm of chromosome 11. Expand
...
1
2
3
4
...