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Genetic analysis of hereditary multiple exostoses in Tunisian families: a novel frame-shift mutation in the EXT1 gene.

Authors: Sfar, Sana  Abid, Abderrazak  Mahfoudh, Wijden  Ouragini, Houyem  Ouechtati, Farah  Abdelhak, Sonia  Chouchane, Lotfi 
Citation: Sfar S, etal., Mol Biol Rep. 2009 Apr;36(4):661-7. doi: 10.1007/s11033-008-9226-3. Epub 2008 Mar 11.
Pubmed: (View Article at PubMed) PMID:18330718
DOI: Full-text: DOI:10.1007/s11033-008-9226-3

Hereditary multiple exostoses (HME) is an autosomal dominant orthopaedic disorder most frequently caused by mutations in the EXT1 gene. The aim of the present study is to determine the underlying molecular defect of HME in two multigenerational Tunisian families with 21 affected members and to examine the degree of intrafamilial variability. Linkage analysis was performed using three microsatellite markers encompassing the EXT1 locus and mutation screening was carried out by direct sequencing. In family 1, evidence for linkage to EXT1 was obtained on the basis of a maximum LOD score of 4.26 at theta = 0.00 with D8S1694 marker. Sequencing of the EXT1 revealed a heterozygous G > T transversion (c.1019G>T) in exon 2, leading to a missense mutation at the codon 340 (p.Arg340Leu). In family 2 we identified a novel heterozygous 1 bp deletion in the exon 1 (c.529_531delA) leading to a premature codon stop and truncated EXT1 protein expression (p.Lys177LysfsX15). This mutation was associated with the evidence of an intrafamilial clinical variability and considered to be a novel disease-causing mutation in the EXT1 gene. These findings provide additional support for the involvement of EXT1 gene in the HME disease.


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CRRD Object Information
CRRD ID: 13208228
Created: 2017-08-08
Species: All species
Last Modified: 2017-08-08
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.