Correction: Association of Rare Genetic Variants in Opioid Receptors with Tourette Syndrome.

[This corrects the article DOI: 10.5334/tohm.464.]

Association of Rare Genetic Variants in Opioid Receptors with Tourette Syndrome

Background: Genes involved in Tourette syndrome (TS) remain largely unknown. We aimed to identify genetic factors contributing to TS in a French cohort of 120 individuals using a combination of hypothesis-driven and exome-sequencing approaches. Methods: We first sequenced exons of SLITRK1-6 and HDC in the TS cohort and subsequently sequenced the exome of 12 individuals harboring rare variants in these genes to find additional rare variants contributing to the disorder under the hypothesis of oligogenic inheritance. We further screened three candidate genes (OPRK1, PCDH10, and NTSR2) preferentially expressed in the basal ganglia, and three additional genes involved in neurotensin and opioid signaling (OPRM1, NTS, and NTSR1), and compared variant frequencies in TS patients and 788 matched control individuals. We also investigated the impact of altering the expression of Oprk1 in zebrafish. Results: Thirteen ultrarare missense variants of SLITRK1-6 and HDC were identified in 12 patients. Exome sequencing in these patients revealed rare possibly deleterious variants in 3,041 genes, 54 of which were preferentially expressed in the basal ganglia. Comparison of variant frequencies altering selected candidate genes in TS and control individuals revealed an excess of potentially disrupting variants in OPRK1, encoding the opioid kappa receptor, in TS patients. Accordingly, we show that downregulation of the Oprk1 orthologue in zebrafish induces a hyperkinetic phenotype in early development. Discussion: These results support a heterogeneous and complex genetic etiology of TS, possibly involving rare variants altering the opioid pathway in some individuals, which could represent a novel therapeutic target in this disorder

Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance

Brain malformations involving the corpus callosum are common in children with developmental disabilities. We identified DCC mutations in four families and five sporadic individuals with isolated agenesis of the corpus callosum (ACC) without intellectual disability. DCC mutations result in variable dominant phenotypes with decreased penetrance, including mirror movements and ACC associated with a favorable developmental prognosis. Possible phenotypic modifiers include the type and location of mutation and the sex of the individual

Étude des facteurs prédictifs de transformation hémorragique de l'infarctus cérébral par tomodensitométrie cérébrale multi-modalités

L'accident ischémique cérébral (AIC) ischémique est un enjeu majeur de santé publique. Son incidence est de 120 000 cas par an en France. La survenue d'une transformation h;morraLzique (TH) est une des complications majeures de l'AIC, à l'origine d'un mauvais pronostic. L'imagerie rzalisze en urgence au CHU de Rouen pour toute suspicion d'AIC est une tomodensitométrie cérébrale (TDMc) multimodalités. Elle permet de mesurer le produit perméabilité-surface (PS), reflet de la perméabilité de la barrière émato-encéphalique, impliquée dans la physiopathologie de la TH. Objectifs : L'objectif de notre travail était de déterminer les facteurs prédictifs radiologiques et cliniques de TH de l'AIC. Matériel et méthode : Il s'aQit d'une étude descriptive, prospective et consécuti\e. mono-centrique, menée du 30 juin 2009 au 31 décembre 2010. concernant les patients accueillis en urgence au CHU de Rouen pour une symptomatologie compatible avec un accident vasculaire cérébral datant de moins de 6 heures. Nous avons recueilli les données cliniques à l'admission, l'évolution clinique immédiate et à 90 jours et les données de la TDMc multi-modalités, dont le PS. IRM cérébrale, ou à défaut la TDMc sans injection, réalisée entre J3 et J5 de l'hospitalisation, permettait de confirmer le diagnostic d'AIC et de mettre en évidence une éventuelle TH au sein de l'infarctus. Résultats : Quatre-vingt six patients ont été inclus. Parmi ces patients 27 ont présenté une TH, dont 11 étaient symptomatiques et 16 asymptomatiques. Un PS > 0.84 ml/100g/min était prédictif de transformation hémorragique. Les autres facteurs prédictifs de TH étaient le volume de la lésion ischémique à la TDM de perfusion et un antécédent de fibrillation auriculaire. Conclusion : Un PS > 0.84 ml/100g/min mesuré à la TDM de perfusion est un facteur prédictif de transformation hémorragique et pourrait aider à la prise en charge des patients à la phase aiguë d'un infarctus cérébral notamment pour la décision de thrombolyse.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

Polaron relaxation in ferroelectric thin films

We report a dielectric relaxation in ferroelectric thin films of the ABO3 family. We have compared films of different compositions with several growth modes: sputtering (with and without magnetron) and sol-gel. The relaxation was observed at cryogenic temperature (T<100K) for frequencies from 100Hz up to 10MHz. This relaxation activation energy is always lower than 200meV. It is very similar to the polaron relaxation that we reported in the parent bulk perovskites. Being independent of the materials size, morphology and texture, this relaxation can be a useful probe of defects in actual integrated capacitors with no need for specific shapin

Polaron relaxation in ferroelectric thin films

We report a dielectric relaxation in ferroelectric thin films of the ABO3 family. We have compared films of different compositions with several growth modes: sputtering (with and without magnetron) and sol-gel. The relaxation was observed at cryogenic temperature (T<100K) for frequencies from 100Hz up to 10MHz. This relaxation activation energy is always lower than 200meV. It is very similar to the polaron relaxation that we reported in the parent bulk perovskites. Being independent of the materials size, morphology and texture, this relaxation can be a useful probe of defects in actual integrated capacitors with no need for specific shapin

Low temperature dielectric relaxation and charged defects in ferroelectric thin films

We report a dielectric relaxation in BaTiO3-based ferroelectric thin films of different composition and with several growth modes: sputtering (with and without magnetron) and sol-gel. The relaxation was observed at cryogenic temperatures (T < 100 K) for frequencies from 100 Hz up to 10 MHz. This relaxation activation energy is always lower than 200 meV and is very similar to the relaxation that we reported in the parent bulk perovskites. Based on our Electron Paramagnetic Resonance (EPR) investigation, we ascribe this dielectric relaxation to the hopping of electrons among Ti3+-V(O) charged defects. Being dependent on the growth process and on the amount of oxygen vacancies, this relaxation can be a useful probe of defects in actual integrated capacitors with no need for specific shaping

Des références partagées pour des alternatives au placement du bébé en danger

National audienceUn groupe de recherche exploratoire, formé lors d’une recherche-action menée par le département d’Ille-et-Vilaine et Askoria, a engagé une réflexion sur « l’accompagnement des enfants et de leurs parents de la grossesse à l’âge de 2 ans ». Son objectif visait à construire des références praxéologiques qui, dans des situations de danger avéré pour le bébé, doivent permettre d’envisager des alternatives à son placement. L’enjeu est de constituer un langage commun entre des professionnels de différents secteurs d’activité afin d’orienter, de manière référencée, les pratiques professionnelles

Predictive Factors of Headache Resolution After Chiari Type 1 Malformation Surgery

International audienceBackgroundHeadache is the main and often isolated symptom of patients with Chiari type 1 malformation (CM1). Classically described as occipital and exacerbated by cough, headaches may be poorly characterized, making it difficult to establish CM1 as the underlying cause. Current guidelines for surgical posterior fossa decompression are undefined. The challenge is to distinguish headaches related to CM1 from headaches coincidentally coexisting with CM1. We aimed to determine predictive factors of headache resolution after surgery and applied to our cohort the Chiari Severity Index, a recently developed predictive prognostic score.MethodsThis retrospective study enrolled 49 patients with CM1 and preoperative headache. Standardized telephone interviews regarding headaches before and after surgery were conducted by the same neurologist; magnetic resonance imaging morphometric analyses were performed by an independent neuroradiologist. Headache resolution was defined as ≥50% reduction in frequency of headache days.ResultsPreoperative factors of headache resolution after multivariate analysis were attack duration <5 minutes (P = 0.001), triggering by Valsalva maneuvers (P = 0.003), severe intensity of attack (P = 0.05), occipital location (P = 0.05), and greater number of headache days per month (P = 0.04). These characteristics are part of International Headache Society diagnostic criteria for headache attributed to CM1. No radiologic predictive factor was demonstrated. Postoperative improvement was inversely correlated with Chiari Severity Index.ConclusionsThis study confirms the relevance of International Headache Society criteria to identify headaches related to CM1. We propose their systematic use in a preoperative questionnaire