Congenital hydrocephalus : new Mendelian mutations and evidence for oligogenic inheritance

Peer reviewe

Performance and Diagnostic Value of Genome-Wide Noninvasive Prenatal Testing in Multiple Gestations.

OBJECTIVE: To evaluate the accuracy and diagnostic value of genome-wide noninvasive prenatal testing (NIPT) for the detection of fetal aneuploidies in multiple gestations, with a focus on dichorionic-diamniotic twin pregnancies. METHODS: We performed a retrospective cohort study including data from pregnant women with a twin or higher-order gestation who underwent genome-wide NIPT at one of the eight Belgian genetic centers between November 1, 2013, and March 1, 2020. Chorionicity and amnionicity were determined by ultrasonography. Follow-up invasive testing was carried out in the event of positive NIPT results. Sensitivity and specificity were calculated for the detection of trisomy 21, 18, and 13 in the dichorionic-diamniotic twin cohort. RESULTS: Unique NIPT analyses were performed for 4,150 pregnant women with a multiple gestation and an additional 767 with vanishing gestations. The failure rate in multiple gestations excluding vanishing gestations ranged from 0% to 11.7% among the different genetic centers. Overall, the failure rate was 4.8%, which could be reduced to 1.2% after single resampling. There were no common fetal trisomies detected among the 86 monochorionic-monoamniotic and 25 triplet cases. Two monochorionic-diamniotic twins had an NIPT result indicative of a trisomy 21, which was confirmed in both fetuses. Among 2,716 dichorionic-diamniotic twin gestations, a sensitivity of 100% (95% CI 74.12-100%) and a specificity of 100% (95% CI 99.86-100%) was reached for trisomy 21 (n=12). For trisomy 18 (n=3), the respective values were 75% (95% CI 30.06-95.44%) sensitivity and 100% (95% CI 99.86-100%) specificity, and for trisomy 13 (n=2), 100% (95% CI 20.65-100%) sensitivity and 99.96% (95% CI 99.79-99.99%) specificity. In the vanishing gestation group, 28 NIPT results were positive for trisomy 21, 18, or 13, with only five confirmed trisomies. CONCLUSION: Genome-wide NIPT performed accurately for detection of aneuploidy in dichorionic-diamniotic twin gestations

Hérédité du cancer du sein : place du médecin généraliste ?

Le cancer du sein touche une femme sur neuf en Belgique. Si chez la majorité des patientes il s’agit d’une affection sporadique, l’hérédité joue un rôle dans 10% à 15% des cas. Dans certaines situations personnelles ou familiales, une analyse génétique peut être proposée aux patient(e)s lors d’une consultation d’oncogénétique. Lorsqu’une mutation germinale est mise en évidence dans une famille, une analyse prédictive peut être proposée aux apparenté(e)s à risque afin de prendre des mesures préventives. Le médecin généraliste, gardien de l’histoire familiale, joue un rôle fondamental tant dans la prise en charge que dans la transmission de l’information à la famille

Mécanismes moléculaires sélectionnés par l'evolution chez les primates pour se protéger vis-a-vis de l'hormone chorio-gonadotrophique.

The constitutive activation of the follitropin receptor (FSHR) could lead to promiscuous toxic activation by placental chorionic gonadotropin (CG) during human pregnancy. This study demonstrated that the evolution of the transmembrane region of the simian FSHR parallels the progressive accumulation of CG copies in the primate genomes. We assist to a purifying selection to keep the FSHR constitutively inactive and thus insensitive to CG.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Comprendre le syndrome d’hyperstimulation ovarienne

info:eu-repo/semantics/publishe

Understanding ovarian hyperstimulation syndrome.

The ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening complication of ovarian stimulation treatments. Severe forms are characterized by a massive ovarian enlargement with the formation of multiple ovarian cysts associated with extravascular fluid shifts resulting in the development of ascites, pleural and/or pericardial effusion. The pathophysiology of the syndrome has not been completely elucidated yet. The vascular fluid leakage is thought to result from an increased capillary permeability of mesothelial surfaces under the action of one or several vasoactive ovarian factor(s) produced by the multiple corpora lutea. The paper focuses on the recent identification of mutations in the FSH receptor gene that display an increased sensitivity to hCG and are responsible for the development of spontaneous OHSS occurring during pregnancy. These findings have shed light for the first time on the molecular basis of the pathophysiology of the spontaneous form of the syndrome. As spontaneous and iatrogenic OHSS share similar pathophysiological sequences including massive recruitment and growth of ovarian follicles, extensive luteinization provoked by hCG, and oversecretion of vasogenic molecules by the corpora lutea, they have also opened new research perspectives for the understanding of the much more frequent iatrogenic OHSS.Journal ArticleReviewinfo:eu-repo/semantics/publishe

Analysis of the nucleoles kinetics within one cell cycle in CHO cells by PCC

info:eu-repo/semantics/publishe

Fibroses pulmonaires familiales et téloméropathies

Les mutations germinales des gènes impliqués dans la biologie des télomères constituent la première cause identifiée de fibrose pulmonaire familiale. La perte de la fonction protectrice de ces structures entraine un arrêt de la réplication cellulaire et un épuisement de certaines sous-populations de cellules, menant au développement possible de fibroses pulmonaires ainsi que des pathologies hématologiques, hépatiques et cutanées. Au niveau pulmonaire, les téloméropathies se manifestent sous forme d’une fibrose précoce et rapidement progressive, menant à l’insuffisance respiratoire terminale. Lors du bilan initial, la présence d’une composante multi-systémique, d’un caractère familial ou d’un âge précoce au diagnostic sont les éléments caractéristiques d’une téloméropathie. La mesure de la longueur des télomères et la recherche de mutations germinales permettent de compléter la mise au point. La prise en charge de ces patients est rendue complexe par la nature rapidement progressive de l’atteinte pulmonaire, le risque majoré d’effets secondaires médicamenteux et l’efficacité limitée des traitements antifibrosants. Les Cliniques universitaires Saint-Luc ont mis au point un trajet de soin spécifique à cette pathologie, avec une collaboration entre les services de pneumologie, d’hématologie et de génétique afin d’offrir une prise en charge optimale. Que savons-nous à ce propos ? Les téloméropathies sont la première cause identifiée de fibrose pulmonaire familiale. Elles se caractérisent par une forme rapidement progressive avec une atteinte multisystémique et un âge de développement précoce. Que nous apporte cet article ? Cet article offre une revue de la littérature publiée sur la fibrose pulmonaire familiale liée aux téloméropathies en reprenant les caractéristiques principales de cette pathologie. Il présente également le trajet de soin mis en place au sein des Cliniques Universitaires Saint-Luc afin de prendre en charge ces patients complexes

Evolutive strategy of TSH receptor to avoid promiscuous activation by hCG during pregnancy

info:eu-repo/semantics/nonPublishe

Importance of basic residues and quaternary structure in the function of MIP-1β: CCR5 binding and cell surface sugar interactions

Chemokines direct immune cells toward sites of infection by establishing a gradient across the extracellular matrix of the tissue. This gradient is thought to be stabilized by ligation of chemokines to sulfated polysaccharides known as glycosaminoglycans (GAGs) that are found on the surface of endothelial and other cells as well as in the tissue matrix. GAGs interact with chemokines and in some cases cause them to aggregate. The interaction between cell surface GAGs and chemokines has also been postulated to play a role in the anti-HIV activity of some chemokines, including MIP-1beta. Since many proteins interact with GAGs by utilizing basic residues, we mutated R18, K45, R46, and K48 in MIP-1beta to investigate the role of these residues in GAG binding and CCR5 function. We find that no single amino acid substitution alone has a dramatic effect on heparin binding, although change at R46 has a moderate effect. However, binding to heparin is completely abrogated in a mutant (K45A/R46A/K48A) in which the entire "40's loop" has been neutralized. A functional study of these mutants reveals that the charged residues in this 40's loop, particularly K48 and R46, are critical mediators of MIP-1beta binding to its receptor CCR5. However, despite the partially overlapping function of the residues in the 40's loop in binding to both CCR5 and heparin, the presence of cell surface sugars does not appear to be necessary for the ability of MIP-1beta to function on its receptor CCR5, as enzymatic removal of GAGs from cells results in little effect on MIP-1beta activity. Because the means by which the chemokine gradient transmits information to the recruited cells is not well defined, we also mutated the basic residues in MIP(9), a truncated form of MIP-1beta that is impaired in its ability to dimerize, to probe whether the quaternary structure of this chemokine influences its ability to bind heparin. None of the truncated variants bound as well as the full-length proteins containing the same mutation, suggesting that the MIP-1beta dimer participates in heparin binding.Journal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.info:eu-repo/semantics/publishe