Breakpoint characterization of large deletions in EXT1 or EXT2 in 10 Multiple Osteochondromas families

<p>Abstract</p> <p>Background</p> <p>Osteochondromas (cartilage-capped bone tumors) are by far the most commonly treated of all primary benign bone tumors (50%). In 15% of cases, these tumors occur in the context of a hereditary syndrome called multiple osteochondromas (MO), an autosomal dominant skeletal disorder characterized by the formation of multiple cartilage-capped bone tumors at children's metaphyses. MO is caused by various mutations in <it>EXT1 </it>or <it>EXT2</it>, whereby large genomic deletions (single-or multi-exonic) are responsible for up to 8% of MO-cases.</p> <p>Methods</p> <p>Here we report on the first molecular characterization of ten large <it>EXT1</it>- and <it>EXT2</it>-deletions in MO-patients. Deletions were initially indentified using MLPA or FISH analysis and were subsequently characterized using an MO-specific tiling path array, allele-specific PCR-amplification and sequencing analysis.</p> <p>Results</p> <p>Within the set of ten large deletions, the deleted regions ranged from 2.7 to 260 kb. One <it>EXT2 </it>exon 8 deletion was found to be recurrent. All breakpoints were located outside the coding exons of <it>EXT1 </it>and <it>EXT2</it>. Non-allelic homologous recombination (NAHR) mediated by <it>Alu</it>-sequences, microhomology mediated replication dependent recombination (MMRDR) and non-homologous end-joining (NHEJ) were hypothesized as the causal mechanisms in different deletions.</p> <p>Conclusions</p> <p>Molecular characterization of <it>EXT1</it>- and <it>EXT2</it>-deletion breakpoints in MO-patients indicates that NAHR between <it>Alu-</it>sequences as well as NHEJ are causal and that the majority of these deletions are nonrecurring. These observations emphasize once more the huge genetic variability which is characteristic for MO. To our knowledge, this is the first study characterizing large genomic deletions in <it>EXT1 </it>and <it>EXT2</it>.</p

Anticoagulation regimes and their influence on the occlusion rate of aneurysms: an experimental study in rabbits.

OBJECTIVE: Our purpose was to determine whether anticoagulation has an influence on the occlusion rate and thromboembolic occurrence in saccular aneurysms treated with Guglielmi detachable coils. METHODS: Aneurysms in the right CCA were created in rabbits. Group 1 served as a control group (n = 6) without embolization or anticoagulation. In Groups 2 to 5, aneurysms were embolized. In Group 2, no anticoagulation was given (n = 5). Group 3 received heparin before the placement of the first coil, then low molecular weight heparin (LMWH) for the next 2 days (n = 7). In Group 4, additional aspirin was administered after 2 days until sacrifice (n = 10). Group 5 received heparin before the placement of the first coil, then a LMHW was administered daily until sacrifice (n = 5). Angiography was performed 3 months after coiling, followed by a histological examination. RESULTS: Histopathological evaluation showed thrombus formation with neovascularization, regardless of the anticoagulation regime used. Only in the group with LMWH over 3 months was the thrombus not focally, properly organized, especially in the dome. The coils in the neck showed, however, the same fibrous scar tissue as in the other groups. CONCLUSION: Anticoagulation with heparin during the first days, followed by aspirin, appears unlikely to affect the occlusion rate in aneurysms. LMWH over a long period, however, could impair thrombus organization. Therefore, in regard to thrombus organization, an anticoagulation regime with aspirin seems to be superior to LMWH. This could play an important role in the prevention of thromboembolic events in humans treated with Guglielmi detachable coils

Long-term results with Matrix coils vs. GDC: an angiographic and histopathological comparison.

INTRODUCTION: The aim of the study was to compare standard platinum Guglielmi detachable coils (GDC) with coated platinum coils (Matrix; both Boston Scientific, Fremont, CA) regarding handling, complications, occlusion and recanalization rate after 3 and 6A months. METHODS: Aneurysms in the right common carotid artery were created in 25 rabbits. The animals were divided into five groups of five animals each. The animals of group 1 (the control group) received no treatment of the induced aneurysms, the animals of groups 2 and 3 (killed at 3 and 6A months) were treated with standard GDC, and the animals of groups 4 and 5 (killed at 3 and 6A months) were treated with Matrix coils. RESULTS: Histopathological evaluation showed organized thrombus formation and connective tissue with neovascularization around the implanted coils in all the treated groups. The achieved occlusion rates in groups 2 and 3 were identical to those in groups 4 and 5. Thus the long-term results of aneurysm treatment with GDC and Matrix coils show no differences regarding occlusion and recanalization rates. The only noticeable difference was the difference in handling. More force was required to pushing the Matrix coils forward through the microcatheter and there was more friction in coil interaction in the aneurysm. CONCLUSION: The bioactive coating of the Matrix coil produces no significant benefit in achieving higher occlusion and lower recanalization rates, and the coil is more difficult to handle. Future bioactive coils must be shown to produce significantly better long-term results than GDC and their ease of handling has to be improved