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Lannoy N.,Cliniques universitaires Saint Luc | Lannoy N.,Catholic University of Louvain | Bandelier C.,Cliniques universitaires Saint Luc | Grisart B.,Institute Of Pathologie Et Of Genetique Ipg | And 5 more authors.
Haemophilia | Year: 2015

Summary: In approximately 90% of mild haemophilia A (HA) patients, a missense mutation can be identified using complete gene sequencing. In this study, multiplex ligation-dependent probe amplification analysis was performed as a second step in 10 French-speaking Belgian with mild HA presenting no detectable causal mutation by complete sequencing of the factor VIII (FVIII) (F8) gene's 26 exons and its 1.2 kb of contiguous promoter sequence. This gene dosage technique enabled the detection of exon 1 duplications of F8 in three apparently unrelated subjects. Using array-comparative genomic hybridization, breakpoint analysis delimited the duplication extent to 210 kb in the F8 intron 1 and VBP1 gene intragenic position. We postulated that the rearrangement responsible for this duplication, never before reported, could be attributed to a symmetrical tandem inversion duplication, resulting in a large 233 kb rearrangement of F8 intron 1. This rearranged intron should lead to the production of a small number of normal mRNA transcripts in relation to the mild HA phenotype. Our analysis of the entire F8 mRNA from index case 1, particularly the segment containing exons 1-9, revealed normal amplification and sequencing. Reduced plasma FVIII antigen levels caused by cross-reacting material is associated with a quantitative deficiency of plasma FVIII. Male patients were unresponsive to desmopressin (1-deamino-8-D-arginine vasopressin). All patients displayed identical F8 haplotypes, despite not being related, which suggests a possible founder effect caused by a 210 kb duplication involving F8 exon 1. © 2015 John Wiley & Sons Ltd214 July 2015 10.1111/hae.12675 Original Article Original Articles Genetics © 2015 John Wiley & Sons Ltd. Source

Debry J.-M.,Institute Of Pathologie Et Of Genetique Ipg
Andrologie | Year: 2010

As well as the other assisted reproductive technologies, insemination with donor sperm has received an abundant legislative framework in Belgium providing the context in which this activity is allowed. According to a law of 2007, we know an access to donor sperm is also open for lesbian and single women. Even if they have to be declined in the multiple points of view of the Belgian society, the National Advisory Ethical Committee proposed in 2004 recommendations for the use of donor sperm. Based on an unusual consensus, it appears that anonymity of the sperm donor must be preserved as long as possible, even if some think that an access to non identifying information (concerning position, philosophy, etc.) should remain accessible if the donor agrees and if it is requested by the patients, mainly if they are lesbian or single. © Springer 2009. Source

Jungels C.,Service de chirurgie | Stefanidis C.,Service de chirurgie | Hackx M.,Service dimagerie medicale | Oana M.,Institute Of Pathologie Et Of Genetique Ipg | Colonval P.,Service de chirurgie
Revue Medicale de Bruxelles | Year: 2015

Malignant melanoma is a rapidly metastatic disease. Metastasis in the small intestine is as such not uncommon, whereas the clinical presentation of obstruction due to intussusception is very rare. We hereafter report the case of a 58-year-old female admitted with general degradation, syndrome of intestinal occlusion and a cervical mass. Imaging studies showed signs suggesting an invagination of the small intestine. A resection of the cervical mass and segmental small intestine resection were performed. Pathological findings revealed a cervical malignant melanoma spread into the small intestine. The diagnosis of intestinal metastasis should therefore be considered in patients with intestinal occlusion and history of melanoma and presenting gastrointestinal symptoms. © A.M.U.B. 2015. Source

Carrasco J.,Grand Hopital de Charleroi GHDC | Gizzi M.,Grand Hopital de Charleroi GHDC | Pairet G.,Cliniques Universitaires St Luc Universitecatholique Of Leuven Ucl | Lannoy V.,Cliniques Universitaires St Luc Universitecatholique Of Leuven Ucl | And 12 more authors.
British Journal of Cancer | Year: 2015

Background:Optimal preoperative treatment before colorectal cancer metastases (CRCM) resection remains unclear. This study evaluated pathological responses (pR) in CRCM resected after chemotherapy alone or combined with angiogenesis or epidermal growth factor receptor (EGFR) inhibitors.Methods:Pathological response was retrospectively evaluated on 264 resected metastases from 99 patients. The proportion of responding metastases after different preoperative treatments was reported and compared. Patient's progression-free survival (PFS) and overall survival (OS) were compared based on pR.Results:The combination of anti-angiogenics with oxaliplatin-based chemotherapy resulted in more pR than when they were combined with irinotecan-based chemotherapy (80% vs 50%; P<0.001). Inversely, the combination of EGFR inhibitors with oxaliplatin-based chemotherapy seemed to induce fewer pR than when they were combined with irinotecan-based treatment (53% vs 72%; P=0.049). Overall survival at 5 years was improved for patients with a pR in all resected metastases compared with those who did not achieve a pR (68.5% vs 32.6%; P=0.023) and this response was the only factor predicting OS in a multivariate analysis.Conclusion:The chemotherapy partner combined with angiogenesis or EGFR inhibitors influenced pR in resected CRCM. In our exploratory analysis anti-angiogenic/oxaliplatin-based regimens and anti-EGFR/irinotecan-based regimens were associated with the highest pR. Prospective randomised trials should be performed to validate these observations. © 2015 Cancer Research UK. All rights reserved. Source

Parker M.J.,Sheffield Childrens Hospital NHS Foundation Trust | Fryer A.E.,Alder Hey Childrens NHS Foundation Trust | Shears D.J.,University of Oxford | Lachlan K.L.,University of Southampton | And 10 more authors.
American Journal of Medical Genetics, Part A | Year: 2015

De novo mutations (DNM) in SYNGAP1, encoding Ras/Rap GTPase-activating protein SynGAP, have been reported in individuals with nonsyndromic intellectual disability (ID). We identified 10 previously unreported individuals with SYNGAP1 DNM; seven via the Deciphering Developmental Disorders (DDD) Study, one through clinical analysis for copy number variation and the remaining two (monozygotic twins) via a research multi-gene panel analysis. Seven of the nine heterozygous mutations are likely to result in loss-of-function (3 nonsense; 3 frameshift; 1 whole gene deletion). The remaining two mutations, one of which affected the monozygotic twins, were missense variants. Each individual carrying a DNM in SYNGAP1 had moderate-to-severe ID and 7/10 had epilepsy; typically myoclonic seizures, absences or drop attacks. 8/10 had hypotonia, 5/10 had significant constipation, 7/10 had wide-based/unsteady gait, 3/10 had strabismus, and 2/10 had significant hip dysplasia. A proportion of the affected individuals had a similar, myopathic facial appearance, with broad nasal bridge, relatively long nose and full lower lip vermilion. A distinctive behavioral phenotype was also observed with aggressive/challenging behavior and significant sleep problems being common. 7/10 individuals had MR imaging of the brain each of which was reported as normal. The clinical features of the individuals reported here show significant overlap with those associated with 6p21.3 microdeletions, confirming that haploinsufficiency for SYNGAP1 is responsible for both disorders. © 2015 Wiley Periodicals, Inc. Source

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