Présentation

Dans les années quatre-vingt et quatre-vingt-dix, les travaux universitaires sur l’écriture et l’analyse des textes ont radicalement modifié les pratiques pédagogiques de classe, de l’école au lycée. Avec la ferme intention d’éreinter la conception élitiste de l’écriture perçue comme un don, ils ont mis en évidence la complexité non seulement de l’écriture, mais encore des dimensions d’un texte, des compétences que réclame l’acte d’écrire et des processus rédactionnels engagés. L’apport didac..

Compte-rendu du séminaire de rencontre entre acteurs des trois territoires (27-28 septembre 2021), projet TORSADES (TerritORialisation de Systèmes Agri-alimentaires DurablES)

métabolisme agri-alimentaire; reconnexion agriculture-alimentation ; études de casConsidérant la nécessité de reconnecter une production agricole durable et la consommation alimentaire, le projet Torsades a pour objectif d’analyser les« contours » (modalités, impacts, contraintes et leviers) de cette reconnexion. Torsades centre son analyse sur l’échelle locale, au travers de trois territoirescontrastés, représentatifs de trois types de situations d’un grand quart nord-est de la France : le périurbain de l’ouest parisien, la Brie dite « laitière » et l’ouestvosgien. Au-delà du travail d’analyse des chercheuses et chercheurs, Torsades ambitionne de fournir des éléments de connaissances et des pistes de réflexion aux acteurs de terrain. Pour soutenir cette dynamique et échanger avec les acteurs, l’équipe du projet Torsades a organisé deux jours de séminaire participatif les 27 et 28 septembre 2021

Analysis of Morbidity and Clinical Implications of Laparoscopic Para-Aortic Lymphadenectomy in a Continuous Series of 98 Patients with Advanced-Stage Cervical Cancer and Negative PET–CT Imaging in the Para-Aortic Area

A series of patients with locally advanced cervical cancer, with no positive para-aortic nodes on positron emission tomography–computed tomography who had undergone a primary laparoscopic para-aortic lymphadenectomy was retrospectively reviewed. Morbidity was limited and the completion of treatment was not delayed when complications occurred

A Parent-of-Origin Effect Impacts the Phenotype in Low Penetrance Retinoblastoma Families Segregating the c.1981C>T/p.Arg661Trp Mutation of RB1

International audienceRetinoblastoma (Rb), the most common pediatric intraocular neoplasm, results from inactivation of both alleles of the RB1 tumor suppressor gene. The second allele is most commonly lost, as demonstrated by loss of heterozygosity studies. RB1 germline carriers usually develop bilateral tumors, but some Rb families display low penetrance and variable expressivity. In order to decipher the underlying mechanisms, 23 unrelated low penetrance pedigrees segregating the common c.1981C>T/p.Arg661Trp mutation and other low penetrance mutations were studied. In families segregating the c.1981C>T mutation, we demonstrated, for the first time, a correlation between the gender of the transmitting carrier and penetrance, as evidenced by Fisher’s exact test: the probability of being unaffected is 90.3% and 32.5% when the mutation is inherited from the mother and the father, respectively (p-value = 7.10−7). Interestingly, a similar correlation was observed in families segregating other low penetrance alleles. Consequently, we investigated the putative involvement of an imprinted, modifier gene in low penetrance Rb. We first ruled out a MED4-driven mechanism by MED4 methylation and expression analyses. We then focused on the differentially methylated CpG85 island located in intron 2 of RB1 and showing parent-of-origin-specific DNA methylation. This differential methylation promotes expression of the maternal c.1981C>T allele. We propose that the maternally inherited c.1981C>T/p.Arg661Trp allele retains sufficient tumor suppressor activity to prevent retinoblastoma development. In contrast, when the mutation is paternally transmitted, the low residual activity would mimic a null mutation and subsequently lead to retinoblastoma. This implies that the c.1981C>T mutation is not deleterious per se but needs to be destabilized in order to reach pRb haploinsufficiency and initiate tumorigenesis. We suggest that this phenomenon might be a general mechanism to explain phenotypic differences in low penetrance Rb families

<i>RB1</i> allelic imbalance in family F5.

<p>The normalized SNaPshot cDNA ratio between the mutant and the wild type alleles are indicated below each carrier individual with corresponding SNaPshot results. The c.1981C>T/p.Arg661Trp mutant allele “T” is indicated in green and the wild type allele “C” is indicated in blue. Dotted symbols: unaffected carriers; half-blackened symbols: unilateral Rb.</p

Methylation analyses of <i>RB1</i> CpG islands using methylation array.

<p>X axis represents the position on chromosome 13. Y axis represents overall methylation level. CpG106 localizing in <i>RB1</i> promoter is shown in green, CpG42 is shown in pink and CpG85 is shown in blue. For each sample, multiple CpGs are located within an island and each dot represents a single result. A: Normal retina. CpG85 showing approximately 50% of methylation. B: Tumor sample. CpG85 displaying a hypermethylated profile.</p

Family F7 segregating the <i>RB1</i> c.1981C>T/p.Arg661Trp mutation.

<p>Genotype is provided for tested members as m/n for heterozygous carriers and n/n for homozygous wild-type. OC indicates obligate carriers. Blackened symbols: bilateral Rb; half-blackened symbols: unilateral Rb; dotted symbols: unaffected carriers; dashed symbols: deceased.</p

Expression imbalance in 20 carriers of the c.1981C>T/p.Arg661Trp mutation.

<p>Transmission in family F5 is detailed <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005888#pgen.1005888.g003" target="_blank">Fig 3</a>. First degree relatives are indicated for the other families. See text for ratio calculation. (*) See <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005888#pgen.1005888.g003" target="_blank">Fig 3</a>.</p

Phenotypical, biological, and molecular heterogeneity of 5α-reductase deficiency: An extensive international experience of 55 patients

Context: In 46,XY disorders of sex development, 5α-reductase deficiency is rare and is not usually the first-intention diagnosis in newborn ambiguous genitalia, contrary to partial androgen insensitivity syndrome. Yet the cause of ambiguous genitalia may guide sex assignment, and rapid, precise diagnosis of 5α-reductase deficiency is essential. Objective: The aim of the study was to describe relevant data for clinical diagnosis, biological investigation, and molecular determination from 55 patients with srd5A2 mutations identified in our laboratory over 20 yr to improve early diagnosis. Setting: The study was performed at Montpellier University Hospital. Patients: We studied a cohort of 55 patients with srd5A2 gene mutations. Main Outcome Measure(s): Genetic analysis of srd5A2 was conducted. Results: Clitoromegaly (49.1%) and microphallus with various degrees of hypospadias (32.7%) were frequent phenotypes. Female external genitalia (7.3%) and isolated micropenis (3.6%) were rare. Seventy-two percent of patients were initially assigned to female gender; five of them (12.5%) switched to male sex in peripuberty. Over 72% of patients were considered for 5α-reductase deficiency diagnosis when the testosterone/dihydrotestosterone cutoff was 10. In 55 patients (with 20 having a history of consanguinity), we identified 33 different mutations. Five have never been reported: p.G32S, p.Y91H, p.G104E, p.F223S, and c.461delT. Homozygous mutations were present in 69.1% of cases, compound heterozygous mutations in 25.5%, and compound heterozygous mutations alone with the V89L polymorphism in 5.4%. Exons 1 and 4 were most affected, with 35.8 and 21.7% mutant alleles per exon, respectively. Conclusions: In the largest cohort to date, we demonstrate a wide spectrum of phenotypes and biological profiles in patients with 5α-reductase deficiency, whatever their geographical or ethnic origins. Copyright © 2011 by The Endocrine Society.SCOPUS: ar.jinfo:eu-repo/semantics/publishe