Diagnostic prénatal et diagnostic pré-implantatoire : arbre décisionnel, nouvelles pratiques ?

Le diagnostic pré-implantatoire (DPI) a pour objectif l’étude des caractéristiques génétiques d’un embryon âgé de trois jours. Il offre ainsi à des couples ayant un risque élevé de transmettre une maladie héréditaire une alternative au diagnostic prénatal (DPN). Si, au début de son application, les pathologies et les couples pris en charge ainsi que le cadre réglementaire du DPI étaient très proches de ceux du DPN, des indications propres au DPI émergent peu à peu. Les pathologies prises en charge, notamment, se diversifient, en particulier dans les pays où l’absence de réglementation autorise toutes les pratiques. Certaines de ces applications ne sont d’ailleurs pas sans poser de sérieux problèmes éthiques. Même en France, où cette activité est particulièrement encadrée, la récente modification de la loi reflète cette évolution.Preimplantation genetic diagnosis (PGD) purpose is to assess the genetic status of 3 day-old embryos. PGD offers thus to couples « at-risk » of a genetic disorder an earlier option to prenatal diagnosis (PND). At the beginning, PGD’s indications, patients and law were very closed to PND, but PGD specificities are gradually raising. Particularly, indications vary considerably in countries where the absence of law authorizes all the practices. Some of these applications are moreover raising serious ethical issues. Even in France, where this activity is particularly supervised, the recent modification to the law marks this evolution

HOX11L2/TLX3 is transcriptionally activated through T-cell regulatory elements downstream of BCL11B as a result of the t(5;14)(q35;q32).

International audienceThe t(5;14)(q35;q32) chromosomal translocation is specifically observed in up to 20% of childhood T-cell acute lymphoblastic leukemia (T-ALL). It affects the BCL11B/CTIP2 locus on chromosome 14 and the RANBP17-TLX3/HOX11L2 region on chromosome 5. It leads to ectopic activation of TLX3/HOX11L2. To investigate the reasons of the association between t(5;14) and T-ALL, we isolated the translocation breakpoints in 8 t(5;14) patients. Sequence analyses did not involve recombinase activity in the genesis of the translocation. We used DNAse1 hypersensitive experiments to locate transcriptional regulatory elements downstream of BCL11B. By transient transfection experiments, 2 of the 6 regions demonstrated cis-activation properties in T cells and were also effective on the TLX3 promoter. Our data indicate that the basis of the specific association between t(5;14) and T-ALL lies on the juxtaposition of TLX3 to long-range cis-activating regions active during T-cell differentiation

Association between nutritional profiles of foods underlying Nutri-Score front-of-pack labels and mortality: EPIC cohort study in 10 European countries.

OBJECTIVE: To determine if the Food Standards Agency nutrient profiling system (FSAm-NPS), which grades the nutritional quality of food products and is used to derive the Nutri-Score front-of-packet label to guide consumers towards healthier food choices, is associated with mortality. DESIGN: Population based cohort study. SETTING: European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from 23 centres in 10 European countries. PARTICIPANTS: 521 324 adults; at recruitment, country specific and validated dietary questionnaires were used to assess their usual dietary intakes. A FSAm-NPS score was calculated for each food item per 100 g content of energy, sugars, saturated fatty acids, sodium, fibre, and protein, and of fruit, vegetables, legumes, and nuts. The FSAm-NPS dietary index was calculated for each participant as an energy weighted mean of the FSAm-NPS score of all foods consumed. The higher the score the lower the overall nutritional quality of the diet. MAIN OUTCOME MEASURE: Associations between the FSAm-NPS dietary index score and mortality, assessed using multivariable adjusted Cox proportional hazards regression models. RESULTS: After exclusions, 501 594 adults (median follow-up 17.2 years, 8 162 730 person years) were included in the analyses. Those with a higher FSAm-NPS dietary index score (highest versus lowest fifth) showed an increased risk of all cause mortality (n=53 112 events from non-external causes; hazard ratio 1.07, 95% confidence interval 1.03 to 1.10, P<0.001 for trend) and mortality from cancer (1.08, 1.03 to 1.13, P<0.001 for trend) and diseases of the circulatory (1.04, 0.98 to 1.11, P=0.06 for trend), respiratory (1.39, 1.22 to 1.59, P<0.001), and digestive (1.22, 1.02 to 1.45, P=0.03 for trend) systems. The age standardised absolute rates for all cause mortality per 10 000 persons over 10 years were 760 (men=1237; women=563) for those in the highest fifth of the FSAm-NPS dietary index score and 661 (men=1008; women=518) for those in the lowest fifth. CONCLUSIONS: In this large multinational European cohort, consuming foods with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher mortality for all causes and for cancer and diseases of the circulatory, respiratory, and digestive systems, supporting the relevance of FSAm-NPS to characterise healthier food choices in the context of public health policies (eg, the Nutri-Score) for European populations. This is important considering ongoing discussions about the potential implementation of a unique nutrition labelling system at the European Union level

Leucemogenèse induite par les fusions NUP98 (étude moléculaire et fonctionnelle de la fusion NUP98-LNP1)

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Etude de la translocation t(X ; 6)(p11; q23) dans les leucémies aigües à basophiles

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

RECHERCHE D'ANOMALIES DANS L'ASSOCIATION CHARGE PAR CYTOGENETIQUE MOLECULAIRE

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Remaniements du gène NUP98 dans les hémopathies malignes humaines

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF