Abstract
EXT1 and EXT2 are two genes responsible for the majority of cases of hereditary multiple exostoses (HME), a dominantly inherited bone disorder. In order to develop an efficient screening strategy for mutations in these genes, we performed two independent blind screens of EXT1 and EXT2 in 34 unrelated patients with HME, using denaturing high-performance liquid chromatography (DHPLC) and fluorescent single-strand conformation polymorphism analysis (F-SSCP). The mutation likely to cause HME was found in 29 (85%) of the 34 probands: in 22 of these (76%), the mutation was in EXT1; seven patients (24%) had EXT2 mutations. Nineteen of these disease mutations have not been previously reported. Of the 42 different amplicon variants identified in total in the cohort, 40 were detected by DHPLC and 39 by F-SSCP. This corresponds to mutation detection efficiencies of 95% and 93% respectively. We have also found that we can confidently distinguish between different sequence variants in the same fragment using F-SSCP but not DHPLC. In light of this, and the similarly high sensitivities of the two techniques, we propose to continue screening with F-SSCP.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Dobson-Stone, C., Cox, R., Lonie, L. et al. Comparison of fluorescent single-strand conformation polymorphism analysis and denaturing high-performance liquid chromatography for detection of EXT1 and EXT2 mutations in hereditary multiple exostoses. Eur J Hum Genet 8, 24–32 (2000). https://doi.org/10.1038/sj.ejhg.5200409
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ejhg.5200409
Keywords
This article is cited by
-
Mutation spectrum of EXT1 and EXT2 in the Saudi patients with hereditary multiple exostoses
Orphanet Journal of Rare Diseases (2021)
-
Detection of three closely located single nucleotide polymorphisms in the EAAT2 promoter: comparison of single-strand conformational polymorphism (SSCP), pyrosequencing and Sanger sequencing
BMC Genetics (2014)
-
Mutations in the EXT1 and EXT2 genes in Spanish patients with multiple osteochondromas
Scientific Reports (2013)
-
Genetic analysis of hereditary multiple exostoses in Tunisian families: a novel frame-shift mutation in the EXT1 gene
Molecular Biology Reports (2009)
-
Direct estimation of per nucleotide and genomic deleterious mutation rates in Drosophila
Nature (2007)