Vicomtes et vicomtés

Au cours du ixe siècle, des vicomtes sont apparus dans tout l’Occident carolingien pour suppléer les comtes dans l’encadrement local des populations, faisant office de lieutenant du comte dans toutes ses fonctions, fiscales, judiciaires et militaires. À partir de ce fait bien connu, les travaux ici présentés mettent en lumière l’évolution ultérieure qui fait apparaître de très nettes distinctions régionales. Rien de commun en effet entre les zones centrales de l’ancien Empire carolingien, où les vicomtes ont disparu ou ont été ravalés au rang de simples châtelains au service d’un pouvoir supérieur, comtal, ducal ou royal, et les marges carolingiennes où les vicomtes ont accédé à un niveau de pouvoir et d’autonomie remarquable. De ces profondes différenciations, résulte une géographie politique originale entre l’Atlantique et les Alpes, entre la France de l’Ouest et les terres catalanes. Rassemblant des spécialistes de l’histoire politique et sociale médiévale, cet ouvrage nous offre à la fois un panorama détaillé et une synthèse sur des entités territoriales illustres comme la vicomté de Béarn, ou plus méconnues comme celle de Marsan

La vérité

Ce deuxième volume de la collection Le Pouvoir symbolique en Occident (1300-1640), publiée conjointement par les Publications de la Sorbonne et l’École française de Rome, contient les actes du troisième colloque international du cycle Les vecteurs de l’idéel qui a été organisé à Rome en 2012 avec la collaboration de l’École française de Rome dans le cadre du programme SAS (Signs and States), un advanced program du European Research Council

The neurodevelopmental and facial phenotype in individuals with a TRIP12 variant

Haploinsufficiency of TRIP12 causes a neurodevelopmental disorder characterized by intellectual disability associated with epilepsy, autism spectrum disorder and dysmorphic features, also named Clark-Baraitser syndrome. Only a limited number of cases have been reported to date. We aimed to further delineate the TRIP12-associated phenotype and objectify characteristic facial traits through GestaltMatcher image analysis based on deep-learning algorithms in order to establish a TRIP12 gestalt. 38 individuals between 3 and 66 years (F = 20, M = 18) - 1 previously published and 37 novel individuals - were recruited through an ERN ITHACA call for collaboration. 35 TRIP12 variants were identified, including frameshift (n = 15) and nonsense (n = 6) variants, as well as missense (n = 5) and splice (n = 3) variants, intragenic deletions (n = 4) and two multigene deletions disrupting TRIP12. Though variable in severity, global developmental delay was noted in all individuals, with language deficit most pronounced. About half showed autistic features and susceptibility to obesity seemed inherent to this disorder. A more severe expression was noted in individuals with a missense variant. Facial analysis showed a clear gestalt including deep-set eyes with narrow palpebral fissures and fullness of the upper eyelids, downturned corners of the mouth and large, often low-set ears with prominent earlobes. We report the largest cohort to date of individuals with TRIP12 variants, further delineating the associated phenotype and introducing a facial gestalt. These findings will improve future counseling and patient guidance

Mutation-specific pathophysiological mechanisms define different neurodevelopmental disorders associated with SATB1 dysfunction.

Whereas large-scale statistical analyses can robustly identify disease-gene relationships, they do not accurately capture genotype-phenotype correlations or disease mechanisms. We use multiple lines of independent evidence to show that different variant types in a single gene, SATB1, cause clinically overlapping but distinct neurodevelopmental disorders. Clinical evaluation of 42 individuals carrying SATB1 variants identified overt genotype-phenotype relationships, associated with different pathophysiological mechanisms, established by functional assays. Missense variants in the CUT1 and CUT2 DNA-binding domains result in stronger chromatin binding, increased transcriptional repression, and a severe phenotype. In contrast, variants predicted to result in haploinsufficiency are associated with a milder clinical presentation. A similarly mild phenotype is observed for individuals with premature protein truncating variants that escape nonsense-mediated decay, which are transcriptionally active but mislocalized in the cell. Our results suggest that in-depth mutation-specific genotype-phenotype studies are essential to capture full disease complexity and to explain phenotypic variability

Mutation-specific pathophysiological mechanisms define different neurodevelopmental disorders associated with SATB1 dysfunction

International audienceWhereas large-scale statistical analyses can robustly identify disease-gene relationships, they do not accurately capture genotype-phenotype correlations or disease mechanisms. We use multiple lines of independent evidence to show that different variant types in a single gene, SATB1, cause clinically overlapping but distinct neurodevelopmental disorders. Clinical evaluation of 42 individuals carrying SATB1 variants identified overt genotype-phenotype relationships, associated with different pathophysiological mechanisms, established by functional assays. Missense variants in the CUT1 and CUT2 DNA-binding domains result in stronger chromatin binding, increased transcriptional repression, and a severe phenotype. In contrast, variants predicted to result in haploinsufficiency are associated with a milder clinical presentation. A similarly mild phenotype is observed for individuals with premature protein truncating variants that escape nonsense-mediated decay, which are transcriptionally active but mislocalized in the cell. Our results suggest that in-depth mutation-specific genotype-phenotype studies are essential to capture full disease complexity and to explain phenotypic variability