L'ascenseur social reste en panne: les performances des élèves issus de l'immigration en Communauté française et en Communauté flamande

Analyse der Gründe der schlechteren schulischen Leistungen von Schülern ausländischer Herkunft. Analyse der PISA-Studie 2006: ungleiche Bildungschancen, Segregation im Bildungswesen, Notwendigkeit von mehr Demokratisierung der Schulen und von mehr sozialer Mobilität.Analysis of the reasons why pupils of migrant origin are less successful at school. Analysis of the 2006 PISA research: inequal opportunities, segregation in education, need for ongoing democratization of schools and for more social mobility

De sociale lift blijft steken

Analyse der Gründe der schlechteren schulischen Leistungen von Schülern ausländischer Herkunft. Analyse der PISA-Studie 2006: ungleiche Bildungschancen, Segregation im Bildungswesen, Notwendigkeit von mehr Demokratisierung der Schulen und von mehr sozialer Mobilität.Analysis of the reasons why pupils of migrant origin are less successful at school. Analysis of the 2006 PISA research: inequal opportunities, segregation in education, need for ongoing democratization of schools and for more social mobility

De sociale lift blijft steken. De prestaties van allochtone leerlingen in de Vlaamse Gemeenschap en de Franse Gemeenschap

info:eu-repo/semantics/publishe

Exome sequencing allows detection of relevant pharmacogenetic variants in epileptic patients

International audienceBeyond the identification of causal genetic variants in the diagnosis of Mendelian disorders, exome sequencing can detect numerous variants with potential relevance for clinical care. Clinical interventions can thus be conducted to improve future health outcomes for patients and their at-risk relatives, such as predicting late-onset genetic disorders accessible to prevention, treatment or identifying differential drug efficacy and safety. To evaluate the interest of such pharmacogenetic information, we designed an "in house" pipeline to determine the status of 122 PharmGKB (Pharmacogenomics Knowledgebase) variant-drug combinations in 31 genes. This pipeline was applied to a cohort of 90 epileptic patients who had previously an exome sequencing (ES) analysis, to determine the frequency of pharmacogenetic variants. We performed a retrospective analysis of drug plasma concentrations and treatment efficacy in patients bearing at least one relevant PharmGKB variant. For PharmGKB level 1A variants, CYP2C9 status for phenytoin prescription was the only relevant information. Nineteen patients were treated with phenytoin, among phenytointreated patients, none were poor metabolizers and four were intermediate metabolizers. While being treated with a standard protocol (10-23 mg/kg/30 min loading dose followed by 5 mg/kg/8 h maintenance dose), all identified intermediate metabolizers had toxic plasma concentrations (20 mg/L). In epileptic patients, pangenomic sequencing can provide information about common pharmacogenetic variants likely to be useful to guide therapeutic drug monitoring, and in the case of phenytoin, to prevent clinical toxicity caused by high plasma levels

Cohorte française de 41 patients porteurs d’une délétion 2q37

International audienceLe locus 2q37 est l’une des régions subtélomériques les plus fréquemment délétées, pouvant être à l’origine du syndrome microdélétionnel 2q37, aussi appelé syndrome d’Ostéodystrophie Héréditaire d’Albright-like (AHO-like) ou syndrome retard mental-brachydactylie (BDMR) (MIM 60043), d’expression clinique variable. Suite à un appel à collaboration nationale, 41 patients porteurs d’une délétion 2q37 isolée ont été recensés. Tous les diagnostics ont été posés par l’analyse chromosomique sur puces à ADN, et confirmés par FISH avec une sonde locus-spécifique 2q37. Les délétions sont de taille variable, de 14kb intragénique DIS3L2 à 9.6 Mb. La majorité des cas est non héritée, de probable survenue de novo. Cette cohorte, pédiatrique et adulte, permet de confirmer la variabilité phénotypique et d’affiner le phénotype post-natal (1 seul cas prénatal). Les deux signes principaux mais inconstants sont les difficultés légères à modérées des apprentissages associées à des troubles comportementaux notamment des difficultés attentionnelles, et la brachydactylie. La morphologie faciale typique précédemment rapportée est fréquente également dans notre cohorte. L’obésité (6/26), le surpoids (3/26), la petite taille (2/29) sont absents dans plus de 70% des cas. L’épilepsie est décrite dans 15% des cas. Les malformations sont le plus souvent cardiaques et rénales, de bon pronostic. D’autres particularités cliniques ont été soulignées (notamment malformations cérébrales non spécifiques, troubles du transit, trouble du sommeil, troubles squelettiques et hyperlaxité). Il s’agit de la plus grosse cohorte de patients non publiés (28/41) décrite à ce jour

EPHA7 haploinsufficiency is associated with a neurodevelopmental disorder

International audienceEphrin receptor and their ligands, the ephrins, are widely expressed in the developing brain. They are implicated in several developmental processes that are crucial for brain development. Deletions in genes encoding for members of the Eph/ephrin receptor family were reported in several neurodevelopmental disorders. The ephrin receptor A7 gene (EPHA7) encodes a member of ephrin receptor subfamily of the protein-tyrosine kinase family. EPHA7 plays a role in corticogenesis processes, determines brain size and shape, and is involved in development of the central nervous system. One patient only was reported so far with a de novo deletion encompassing EPHA7 in 6q16.1. We report 12 additional patients from nine unrelated pedigrees with similar deletions. The deletions were inherited in nine out of 12 patients, suggesting variable expressivity and incomplete penetrance. Four patients had tiny deletions involving only EPHA7, suggesting a critical role of EPHA7 in a neurodevelopmental disability phenotype. We provide further evidence for EPHA7 deletion as a risk factor for neurodevelopmental disorder and delineate its clinical phenotype

A French multicenter study of over 700 patients with 22q11 deletions diagnosed using FISH or aCGH

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Heterozygous deletion of the LRFN2 gene is associated with working memory deficits

International audienceLearning disabilities (LDs) are a clinically and genetically heterogeneous group of diseases. Array-CGH and high-throughput sequencing have dramatically expanded the number of genes implicated in isolated intellectual disabilities and LDs, highlighting the implication of neuron-specific post-mitotic transcription factors and synaptic proteins as candidate genes. We report a unique family diagnosed with autosomal dominant learning disability and a 6p21 microdeletion segregating in three patients. The 870 kb microdeletion encompassed the brain-expressed gene LRFN2, which encodes for a synaptic cell adhesion molecule. Neuropsychological assessment identified selective working memory deficits, with borderline intellectual functioning. Further investigations identified a defect in executive function, and auditory-verbal processes. These data were consistent with brain MRI and FDG-PET functional brain imaging, which, when compared with controls, revealed abnormal brain volume and hypometabolism of gray matter structures implicated in working memory. We performed electron microscopy immunogold labeling demonstrating the localization of LRFN2 at synapses of cerebellar and hippocampal rat neurons, often associated with the NR1 subunit of N-methyl-D-aspartate receptors (NMDARs). Altogether, the combined approaches imply a role for LRFN2 in LD, specifically for working memory processes and executive function. In conclusion, the identification of familial cases of clinically homogeneous endophenotypes of LD might help in both the management of patients and genetic counseling for families

1p36 deletion syndrome: Review and mapping with further characterization of the phenotype, a new cohort of 86 patients

International audienceChromosome 1p36 deletion syndrome (1p36DS) is one of the most common terminaldeletion syndromes (incidence between 1/5000 and 1/10,000 live births in theAmerican population), due to a heterozygous deletion of part of the short arm ofchromosome 1. The 1p36DS is characterized by typical craniofacial features, develop-mental delay/intellectual disability, hypotonia, epilepsy, cardiomyopathy/congenitalheart defect, brain abnormalities, hearing loss, eyes/vision problem, and short stature.The aim of our study was to (1) evaluate the incidence of the 1p36DS in the Frenchpopulation compared to 22q11.2 deletion syndrome and trisomy 21; (2) review thepostnatal phenotype related to microarray data, compared to previously publish pre-natal data. Thanks to a collaboration with the ACLF (Association des Cytogénéticiensde Langue Française), we have collected data of 86 patients constituting, to the bestof our knowledge, the second-largest cohort of 1p36DS patients in the literature. Weestimated an average of at least 10 cases per year in France. 1p36DS seems to bemuch less frequent than 22q11.2 deletion syndrome and trisomy 21. Patients pre-sented mainly dysmorphism, microcephaly, developmental delay/intellectual disabil-ity, hypotonia, epilepsy, brain malformations, behavioral disorders, cardiomyopathy,or cardiovascular malformations and, pre and/or postnatal growth retardation. Car-diac abnormalities, brain malformations, and epilepsy were more frequent in distaldeletions, whereas microcephaly was more common in proximal deletions. Mappingand genotype–phenotype correlation allowed us to identify four critical regionsresponsible for intellectual disability. This study highlights some phenotypic variabil-ity, according to the deletion position, and helps to refine the phenotype of 1p36DS,allowing improved management and follow-up of patient