Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
ISSN: 0012-8252

hal-01671832
https://hal-univ-rochelle.archives-ouvertes.fr/hal-01671832
DOI : 10.1016/j.earscirev.2016.12.005

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Treacher Collins/Franceschetti syndrome (TCS; OMIM 154500) is a disorder of craniofacial development belonging to the heterogeneous group of mandibulofacial dysostoses. TCS is classically characterized by bilateral mandibular and malar hypoplasia, downward-slanting palpebral fissures, and microtia. To date, three genes have been identified in TCS:,TCOF1, POLR1D, and POLR1C. We report a clinical and extensive molecular study, including TCOF1, POLR1D, POLR1C, and EFTUD2 genes, in a series of 146 patients with TCS. Phenotype-genotype correlations were investigated for 19 clinical features, between TCOF1 and POLR1D, and the type of mutation or its localization in the TCOF1 gene. We identified 92/146 patients (63%) with a molecular anomaly within TCOF1, 9/146 (6%) within POLR1D, and none within POLR1C. Among the atypical negative patients (with intellectual disability and/or microcephaly), we identified four patients carrying a mutation in EFTUD2 and two patients with 5q32 deletion encompassing TCOF1 and CAMK2A in particular. Congenital cardiac defects occurred more frequently among patients with TCOF1 mutation (7/92, 8%) than reported in the literature. Even though TCOF1 and POLR1D were associated with extreme clinical variability, we found no phenotype-genotype correlation. In cases with a typical phenotype of TCS, 6/146 (4%) remained with an unidentified molecular defect.
ISSN: 1098-3600

hal-01134364
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134364
DOI : 10.1038/gim.2015.29
PUBMED : 25790162

Éditeur(s) : HAL CCSD
Résumé : International audience
Background Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. Methods We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. Results We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. Conclusions We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. Trial registration numbers NCT01746121 and NCT02397824
Journal of Medical Genetics

hal-01272929
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01272929
DOI : 10.1136/jmedgenet-2015-103302
PUBMED : 26502894

Éditeur(s) : HAL CCSD Paris : Muséum national d'histoire naturelle
Résumé : International audience
The chromosomal diversity within six species of Mormyridae belonging to six different genera (Gnathonemus petersii, Marcusenius moorii, Ivindomyrus obdenboschi, Brienomyrus sp., Stomatorhinus walkeri and Petrocephalus microphthalmus) is investigated for the first time. These species have a conserved diploid chromosome number of 2n = 50 (except G. petersii 2n = 48) but different chromosome formulae, essentially involving pericentric inversions. C-banding has been used for the localization of heterochromatin. For a deeper interspecific comparison, several molecular markers were localized in the chromosomes by fluorescence in situ hybridization (FISH): a 18S rDNA probe; a microsatellite probe (GAA)(10), and a telomeric probe (TTAGGG)(7). The distribution of the 18S rDNA patterns, in particular, shows an amazing specific diversity, confirming a rapid radiation accompanied by major chromosome rearrangements.
ISSN: 0399-0974

hal-01544756
https://hal.archives-ouvertes.fr/hal-01544756

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
OBJECTIVES: Tracheobronchial stenosis (TBS) is noted in 12-23% of patients with granulomatosis with polyangiitis (GPA), and includes subglottic stenosis and bronchial stenosis. We aimed to analyse the endoscopic management of TBS in GPA and to identify factors associated with the efficacy of endoscopic interventions. METHODS: We conducted a French nationwide retrospective study that included 47 patients with GPA-related TBS. RESULTS: Compared with patients without TBS, those with TBS were younger, more frequently female and had less frequent kidney, ocular and gastrointestinal involvement and mononeuritis multiplex. Endoscopic procedures included 137 tracheal and 50 bronchial interventions, mainly endoscopic dilatation, local steroid injection and conservative laser surgery, and less frequently stenting. After the first endoscopic procedure, the cumulative incidence of endoscopic treatment failure was 49% at 1 year, 70% at 2 years and 80% at 5 years. Factors significantly associated with a higher cumulative incidence of treatment failure were a shorter time from GPA diagnosis to endoscopic procedure [hazard ratio (HR) 1.08 (95% CI 1.01, 1.14); P = 0.01] and a bronchial stenosis [HR 1.96 (95% CI 1.28, 3.00); P = 0.002]. A prednisone dose ≥30 mg/day at the time of the procedure was associated with a lower cumulative incidence of treatment failure [HR 0.53 (95% CI 0.31, 0.89); P = 0.02]. CONCLUSION: TBS represents severe and refractory manifestations with a high rate of restenosis. High-dose systemic CSs at the time of the procedure and increased time from GPA diagnosis to bronchoscopic intervention are associated with a better event-free survival. In contrast, bronchial stenoses are associated with a higher rate of restenosis than subglottic stenosis.
ISSN: 1462-0324

hal-01155105
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01155105
DOI : 10.1093/rheumatology/kev129
PUBMED : 26001634

Éditeur(s) : HAL CCSD
Résumé : International audience

Background. Projections of medical demography show a decrease of number of doctors who practice in a rural setting and a low amount of general practitioners’ facilities.

Aim. To explore residents’ career choices and to determine their terms to settle in rural areas.
Methods. Qualitative study by groups interviews in five French cities with total of 33 residents. Thematic analysis was performed using the NVivo® software.
Results. Personal life strongly influenced residents’ career choices with a strong desire of free time. Residents considered working among a team rather than in a traditional group practice. They were interested by a practice in rural setting but countryside perceived as too far from urban centres and lacking of access to services. They also imagined the practice conditions as difficult and solitary. Many residents intended practicing in a “semi-rural” setting, the description of which could match with a significant part of the rural area.
Conclusion. If this declared craze for practice in “semi-rural” setting was confirmed, forecasts for some rural areas could be relativized. Public authorities’ attention should then be focused on rural areas far from urban centres and on territories characterized by lonesome medical practice.

Contexte. Les projections en termes de démographie médicale montrent une diminution du nombre de médecins exerçant en zone rurale, avec un faible nombre d’installations.
Objectif. Explorer les souhaits d’exercice des internes et recueillir leurs conditions pour exercer en zone rurale.
Méthode. Étude qualitative par entretiens collectifs dans cinq villes de France auprès de 33 internes. L’analyse thématique a été réalisée à l’aide du logiciel NVivo®.
Résultats. La vie personnelle influençait fortement les souhaits d’exercice, avec un désir de préserver du temps libre. Les internes envisageaient un exercice en équipe, au-delà de l’exercice de groupe traditionnel. Ils étaient intéressés par l’exercice en milieu rural, mais le territoire rural leur apparaissait sans accès aux services et très éloigné des pôles urbains. Ils se représentaient également des conditions d’exercice difficiles et solitaires. De nombreux internes se projetaient dans un exercice en « semi-rural », dont la description pourrait correspondre à une partie non négligeable de l’espace rural.
Conclusion. Si cet engouement déclaré pour l’exercice en semi-rural venait à se confirmer, ces projections concernant certaines zones rurales pourraient être relativisées. L’attention des pouvoirs publics devrait alors se concentrer sur les zones rurales éloignées des pôles urbains et les territoires marqués par un exercice médical solitaire prédominant.

ISSN: 0998-3953

hal-01654623
https://hal.archives-ouvertes.fr/hal-01654623
OKINA : ua16504

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Pyrethroid insecticides are widely used in agriculture and in homes. Despite the neurotoxicity of these insecticides at high doses, few studies have examined whether lower-level exposures could adversely affect children's neurodevelopment. The PELAGIE cohort included 3421 pregnant women from Brittany, France between 2002 and 2006. When their children reached their sixth birthday, 428 mothers from the cohort were randomly selected, successfully contacted and found eligible. A total of 287 (67%) mothers agreed to participate with their children in the neuropsychological follow-up. Two cognitive domains were assessed by the Wechsler Intelligence Scale for Children: verbal comprehension and working memory. Five pyrethroid and two organophosphate insecticide metabolites were measured in maternal and child first-void urine samples collected between 6 and 19 gestational weeks and at 6 years of age, respectively. Linear regression models were used to estimate associations between cognitive scores and urinary pyrethroid metabolite concentrations, adjusting for organophosphate metabolite concentrations and potential confounders. Maternal prenatal pyrethroid metabolite concentrations were not consistently associated with any children's cognitive scores. By contrast, childhood 3-PBA and cis-DBCA concentrations were both negatively associated with verbal comprehension scores (P-trend = 0.04 and P-trend < 0.01, respectively) and with working memory scores (P-trend = 0.05 and P-trend < 0.01, respectively). No associations were observed for the three other childhood pyrethroid metabolite concentrations (4-F-3-PBA, cis-DCCA, and trans-DCCA). Low-level childhood exposures to deltamethrin (as cis-DBCA is its principal and selective metabolite), in particular, and to pyrethroid insecticides, in general (as reflected in levels of the 3-PBA metabolite) may negatively affect neurocognitive development by 6 years of age. Whatever their etiology, these cognitive deficits may be of importance educationally, because cognitive impairments in children interfere with learning and social development. Potential causes that can be prevented are of paramount public health importance
ISSN: 0160-4120

hal-01162374
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162374
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162374/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162374/file/Pyrethroid%20insecticide%20exposure.pdf
DOI : 10.1016/j.envint.2015.05.009

Éditeur(s) : HAL CCSD
Résumé : 16 p.
National audience
The objective of this paper is to present an approach for experimenting territorial prospective analysis based on spatial modelling. This approach is carried out in the framework of the DESCARTES project which aims at developing a spatial simulation tool to support the design and analysis of different scenarios for land-use allocation in Reunion Island in terms of environmental services. The spatial modelling tool is composed of two complementary applications: (i) the Ocelet modelling language and its land dynamics simulation environment, and (ii) the Margouill@ platform. The first demonstrator, a model of farm land consumption by urbanization, was developed and presented during workshops in order to test the role of the spatial simulation tool in support of a collaborative innovation process among stakeholders, and to foster new research on social learning, spatial simulation of environmental services, and scale change issues.
L'objectif de cet article est de présenter une démarche de construction d'un exercice de prospective territoriale basé sur un outil de modélisation spatiale. Cette démarche est mise en œuvre dans le cadre du projet ANR DESCARTES dont l'objectif est de construire un outil de simulation cartographique pour analyser différents scénarios d'affectation de l'usage des sols à l'Ile de La Réunion, en termes de services environnementaux. La plateforme de simulation cartographique est composée de deux applications complémentaires (i) le langage de modélisation Ocelet et son environnement de simulation de paysages dynamiques, et (ii) la plateforme Margouill@. Le développement puis la présentation, en atelier, d'un premier démonstrateur sur la consommation des terres agricoles par l'urbanisation a permis de tester l'outil cartographique comme support d'un processus d'innovation collective entre les parties prenantes, et d'ouvrir de nouveaux champs de recherche sur l'analyse de la démarche par les apprentissages, la spatialisation et la simulation prospective des services écosystémiques, et la prise en compte du changement d'échelle.
Acte de la Conférence Internationale de Géomatique et d'Analyse Spatiale
Brest, France

cirad-00850243
http://hal.cirad.fr/cirad-00850243
http://hal.cirad.fr/cirad-00850243/document
http://hal.cirad.fr/cirad-00850243/file/SAGEO-Brest2013-version_finale.pdf