A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement.

BACKGROUND: Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. METHODS: We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. RESULTS: We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. CONCLUSIONS: We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. TRIAL REGISTRATION NUMBERS: NCT01746121 and NCT02397824.journal articleresearch support, non-u.s. gov't2016 Feb2015 10 26importe

Oxygen therapy in hypoxaemic failure to subjects who breathe spontaneously : how can we improve oxygen supplementation ?

The objective of this thesis was to analyse each stage of the O2 supplementation during oxygen therapy in an emergency. This thesis aimed to understand and improve the quality of the management of hypoxaemia patients supplemented with oxygen and ventilating spontaneously. This thesis describes the following research work carried out: Firstly, by deepening knowledge about the precision and accuracy of O2 supplementation systems (rotameters, flowmeters, Oxygen Flow Restrictor) Secondly, we conducted a bench study to verify the accuracy of a predictive formula of the Fraction inspired in O2 of our design. Thirdly, we conducted two studies on the use of an oxygen mask of our conception: The Double Trunk Mask. On the one hand as an oxygen enricher in oxygenated patients using a high flow nasal cannula, and on the other hand in patients oxygenated by a nasal cannula with a low flow. The Double Trunk Mask improves the quantity of oxygen administered without clinical increasing the PaCO2 value.(MOTR - Sciences de la motricité) -- UCL, 202

Implication des gènes Egr1 et Egr2 dans la morphogenèse des tendons chez les vertébrés

Nous avons utilisé les connaissances acquises chez la drosophile pour appréhender l aspect moléculaire de la formation des tendons chez les vertébrés. Chez la drosophile, le gène Stripe est un des acteurs majeurs de la spécification et de la différenciation des tendons. Il est nécessaire et suffisant pour induire l expression de tout un groupe de gènes spécifiques des tendons. Nous avons établi que ses orthologues chez les vertébrés (Egr1 et Egr2) sont eux aussi exprimés dans les tendons et que leur surexpression chez l embryon d oiseau (tube neural) induit l expression de différents gènes cibles liés aux tendons: Scx, EphA4, ColI V et XII. Nous avons ensuite mis en évidence que le Fgf4 connu pour induire l expression des marqueurs majeurs des tendons que sont Scx et tenascin induisait aussi rapidement l expression de Egr1 et Egr2 puis plus tardivement celle des gènes EphA4, ColI V et XII. Enfin si l analyse des mutants de ces gènes n a révélé aucun défaut au niveau de la morphologie des tendons et de l expression des gènes étudiés excepté pour EphA4 c est qu une redondance fonctionnelle de ces deux gènes n est pas à exclure. Nos résultats viennent renforcer le parallèle existant entre la formation des tendons chez les vertébrés et chez la drosphile.PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Administration of Supplemental Oxygen.

To the Editor : Rengasamy et al. address the administration of supplemental oxygen in their video and the associated print supplement (July 15 issue).1 We would like to emphasize the use of two techniques that allow improved oxygenation in nonintubated patients with hypoxemia. [...

Response to correspondence: "Interferon alpha might be an alternative therapeutic choice for refractory neuro-Behçet's disease" - Authors reply.

Dear Editor, We thank Dr. Bolek and colleagues (Bolek et al., 2018) for their appropriate comments about the case report paper we recently published (London et al., 2018) on a patient with lethal neuro-Behçet's disease (NBD) after repeated failure of currently available therapies (steroids, azathioprine, cyclophosphamide, TNF-alpha and IL-6 blockers). We fully agree with Dr Bolek and colleagues that interferon-alpha (IFN-α) could be a potential alternative treatment option for refractory NBD. As pointed out in the paper, controlled or comparative studies on NBD treatment are lacking, thereby rendering the choice of therapy based on expert opinions and small patients’ series. [...

Aglia tau (Linné 1758) : Génétique de la forme ferenigra (Thierry-Mieg 1884)

peer reviewedCette etude se propose d'étudier la génétique de la forme ferenigra d'Aglia tau par des élevages sur plusieures générations. Ces élevages vont permettre de mettre en évidence plusieurs aspects interessant de cette forme rare tant au niveau de la coloration des imagos que de leurs comportement. il permettra enfin d'emettre une nouvelle hypothèse quand à la génétique de cette espéce

Interprétation des principales anomalies de la moelle épinière

n/