Made available in DSpace on 2014-06-11T19:29:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2003-04-29Bitstream added on 2014-06-13T18:58:29Z : No. of bitstreams: 1 amaral_lrog_me_assis.pdf: 523684 bytes, checksum: 4e563b05de50276e16bc28e6de83079e (MD5) / Os acidentes infantis constituem um problema de saúde pública, causam mortes, deixam seqüelas físicas e psicológicas. A cada ano, 160 mil crianças e adolescentes brasileiros morrem ou se tornam incapazes, vítimas de acidentes. O estudo dos acidentes infantis mostra-se complexo na medida em que deve contemplar fatores sociais e contextuais além das motivações psicológicas, individuais, muitas vezes inconscientes do acidentado. O suporte teórico deste estudo teve como base contribuições da teoria psicanalítica e da teoria crítica. A presente pesquisa teve como objetivo entender os acidentes infantis domésticos, em crianças atendidas, no ano de 2000, pelo Pronto-Socorro do Hospital Escola de Maringá-PR. Os participantes foram oito crianças acidentadas na faixa etária de zero a dez anos, com histórico de reincidência, selecionados após um levantamento em 10.944 prontuários. Foram também realizadas entrevistas com pais ou responsáveis pela criança acidentada e com quatro médicos pediatras e uma enfermeira vinculada ao Programa Governamental Saúde da Família. As entrevistas com os profissionais tiveram o objetivo de compreender a visão que estes têm sobre os acidentes infantis. A análise dos dados foi realizada a partir de quatro grandes determinantes, a saber: o acidente como acontecimento casual, o acidente como conseqüência do descuido ou negligência do adulto cuidador, o acidente como manifestação da violência física contra a criança e o acidente como um traço depressivo da criança. Os resultados permitiram associar os acidentes a fatores sociais, biológicos, de gênero e psicológicos. Em muitos momentos os acidentes têm servido para ocultar a depressão... / The infantile accidents constitute a public health problem, cause deaths, and let physical and psychological sequels. Each year 160 thousand Brazilian children and adolescents die or become disabled, victims of accidents. The study on infantile accidents is complex considering that they must embrace social and contextual factors, besides the casualty's sometimes unconscious psychological and individual motivations. This study theoretical support was based on contributions of both the psychoanalytic and critical theories. This research aimed at understanding the domestic infantile accidents of children attended in 2000 by the first-aid clinic of the School Hospital from Maringá city, state of Paraná. The participants were eight children who had suffered an accident between zero to ten year of age, with relapse history, selected after a research in 10.944 handbooks. Interviews with the parents or responsible for the children who had suffered the accident, and with four pediatric doctors and a nurse linked to the Family's Health Governmental Program have been performed. The interviews with the professionals aimed at understanding their point of view concerning the infantile accidents. The data analysis was based on four determinants: the accident as a casual event, the accident as a consequence of the carelessness or negligence of the adult responsible for the children, the accident as the manifestation of the physical violence against the child, and the accident as a depressive profile of the child. The findings allowed us to associate the accidents to psychological, sex, biological and social factors. Many times the accident have contributed to hide the depression, the negligence, and the violence against the child, assuming different meanings... (Complete abstract, click electronic access below)

Anomalies de structure du génome et Déficience Intellectuelle : Recherche des gènes candidats de Déficience intellectuelle en utilisant l'analyse chromosomique sur microréseau d'ADN pangénomique 180K et l'analyse chromosomique sur microréseau d'ADN de haute résolution 1M ciblée des gènes candidats de Déficience intellectuelle. L'analyse chromosomique sur microréseau d'ADN (ACM) de haute résolution est une innovation technologique puissante afin de détecter les aberrations chromosomiques concernant les variations du nombre de copies. En utilisant l'ACM 180K, l'ACM 1M et la PCR quantitative, nous avons identifié les 5 variations du nombre de copies (CNV) intragéniques pathogènes de novo impliquant les gènes : RUNX1T1, KIAA1468, FABP7, ZEB2 (syndrome de Mowat-Wilson) et ANKRD11 (syndrome de KBG). Les 5 patients ayant une DI et une dysmorphie faciale. L'ACM 180K a révélé une délétion d'une taille de 92 kb emportant le gène KIAA1468 candidat pour le syndrome de West chez un enfant de 3 ans présentant une DI sévère et une encéphalopathie épileptique infantile précoce. Le criblage des mutations du gène KIAA1468 a été réalisé chez 35 patients atteints de syndrome de West. Un variant intronique c.2761-7 T>C et un variant faux-sens hérité de la mère c.3547 G>A avec signification clinque inconnue ont été identifiés. En utilisant des approches par l'ACM 1M de haute résolution chez 45 patients atteints de DI idiopathique modérée à sévère, un seul CNV causal a été identifié, une délétion intragénique d'une taille de 28.37 kb du gène ZEB2. Notre étude confirme une fréquence très faible des délétions/duplications intragéniques avec la détection d'une seule aberration chromosomique (1/45). En conclusion, si la fréquence des mutations ponctuelles est élevée, nous avons également souligné l'application de la technique de séquençage à haut débit avec un rendement diagnostique jusqu'à 45%-55% des cas de DI sévère idiopathique chez lesquels aucun CNV n'a été détecté sur ACM / Chromosomal structural abnormalities and Intellectual Disability : In search of intellectual disability candidate genes by using pangenomic comparative genomic hybridization 180 K and high resolution comparative genomic hybridization 1M targeting intellectual disability candidate gene.High resolution microarray-based comparative genomic hybridization (a-CGH) has been a powerful technical innovation in order to detect submicroscopic chromosomal aberrations related to copy number variations. By using a-CGH 180K, 1M high resolution a-CGH and quantitative PCR, we have identified 5 pathogenic intragenic copy number variations (CNVs) de novo : RUNX1T1, KIAA1468, FABP7, ZEB2 (Mowat-Wilson syndrome) and ANKRD11 (KBG syndrome). All five patients had intellectual disability (ID) and facial dysmorphism. Interestingly, a-CGH 180K has revealed a 92 kb deletion of a candidate gene KIAA1468 for West syndrome in a 3 year-old boy with severe ID and early infantile epileptic encephalopathy. Mutational screening for candidate gene KIAA1468 was performed in 35 patients with West syndrome. An intronic variant c.2761-7 T>C and a non synonymous maternally inherited variant c.3547 G>A with unknown clinical significance were identified. By using 1M high-resolution a-CGH approach in 45 patients presenting moderate to severe idiopathic ID, only one causal CNV was identified, a 28.37 kb intragenic ZEB2 deletion. Our study has confirmed the low frequency of intragenic deletion/duplication with the detection of only one chromosomal aberration (1/45). In conclusion, providing that the high frequency of intragenic point mutation, we also stressed the application of next-generation sequencing technology with 45-55% diagnostic yield in patients with idiopathic severe ID in case of no apparent CNV(s) on high-resolution a-CGH

Made available in DSpace on 2016-04-28T20:40:07Z (GMT). No. of bitstreams: 1 Marizilda Ferreira Pugliesi.pdf: 354480 bytes, checksum: fa94418a1b59c3231622569cc61e61b5 (MD5) Previous issue date: 2009-06-10 / This work argues the attendance of the Infantile Psychosis in a Health Public Institution, which constitutes a model of global attendance of children and teenagers, with their relatives, summarized in principles of interdisciplinary and the joint with other services of the community. It is placed in a proposal of an extented clinic, implied with the affirmation of the life in its creative power. I intend to study the game of the relations established between mothers and children who present with a pathological defensive organization, which consists in the infantile psychosis. Meanwhile, it is in the space of the kitchen where they meet each other that, leaving of lived situations, and where they choose recipes and all the unfolding elapses from them. It is in a kitchen where the flavors are, where it constitutes the knowledge. We live intense and tense moments through tears, slaps, beans or lemon cake. An established programming does not exist previously. To each meeting it creates an event and a power to affect and to be affected. To capture the signals that emerge without explaining them or interpret them, but mapping its displacements, in a game of passages and becomes, makes possible that something of new occurs, searching exits for a possible existence / Este trabalho discute o atendimento da Psicose Infantil numa Instituição Pública de Saúde, que constitui um modelo de atendimento global à criança e ao adolescente, junto com seus familiares, pautado por princípios de interdisciplinaridade e da articulação com outros serviços da comunidade. Situa-se numa proposta de uma clínica mais ampla, implicada com a afirmação da vida em sua potência criativa. Pretendo estudar o jogo das relações estabelecidas entre mães e crianças que se apresentam com uma organização defensiva patológica, o que se constitui na psicose infantil. E é no espaço da cozinha onde se dão os encontros que, partindo de situações vivenciadas, se escolhem as receitas culinárias e todo o desdobramento que decorre daí. É numa cozinha onde os sabores estão presentes, que se constituem saberes. Vivemos momentos intensos e tensos através de choros, tapas, feijão de corda ou bolo de limão. Não existe uma programação previamente estabelecida. A cada encontro cria-se um acontecimento e um poder de afetar e ser afetado. Capturar os sinais que emergem sem explicá-los ou interpreta-los, mas cartografando seus deslocamentos, num jogo de trajetos e devires, possibilita que algo de novo ocorra, buscando saídas para uma existência possível

Orientador: Olga Ceciliato Mattioli / Banca: Ana Teresa de Abreu Ramos Cerqueira / Banca: Maria Lúcia Boarine / Resumo: Os acidentes infantis constituem um problema de saúde pública, causam mortes, deixam seqüelas físicas e psicológicas. A cada ano, 160 mil crianças e adolescentes brasileiros morrem ou se tornam incapazes, vítimas de acidentes. O estudo dos acidentes infantis mostra-se complexo na medida em que deve contemplar fatores sociais e contextuais além das motivações psicológicas, individuais, muitas vezes inconscientes do acidentado. O suporte teórico deste estudo teve como base contribuições da teoria psicanalítica e da teoria crítica. A presente pesquisa teve como objetivo entender os acidentes infantis domésticos, em crianças atendidas, no ano de 2000, pelo Pronto-Socorro do Hospital Escola de Maringá-PR. Os participantes foram oito crianças acidentadas na faixa etária de zero a dez anos, com histórico de reincidência, selecionados após um levantamento em 10.944 prontuários. Foram também realizadas entrevistas com pais ou responsáveis pela criança acidentada e com quatro médicos pediatras e uma enfermeira vinculada ao Programa Governamental Saúde da Família. As entrevistas com os profissionais tiveram o objetivo de compreender a visão que estes têm sobre os acidentes infantis. A análise dos dados foi realizada a partir de quatro grandes determinantes, a saber: o acidente como acontecimento casual, o acidente como conseqüência do descuido ou negligência do adulto cuidador, o acidente como manifestação da violência física contra a criança e o acidente como um traço depressivo da criança. Os resultados permitiram associar os acidentes a fatores sociais, biológicos, de gênero e psicológicos. Em muitos momentos os acidentes têm servido para ocultar a depressão... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The infantile accidents constitute a public health problem, cause deaths, and let physical and psychological sequels. Each year 160 thousand Brazilian children and adolescents die or become disabled, victims of accidents. The study on infantile accidents is complex considering that they must embrace social and contextual factors, besides the casualty's sometimes unconscious psychological and individual motivations. This study theoretical support was based on contributions of both the psychoanalytic and critical theories. This research aimed at understanding the domestic infantile accidents of children attended in 2000 by the first-aid clinic of the School Hospital from Maringá city, state of Paraná. The participants were eight children who had suffered an accident between zero to ten year of age, with relapse history, selected after a research in 10.944 handbooks. Interviews with the parents or responsible for the children who had suffered the accident, and with four pediatric doctors and a nurse linked to the Family's Health Governmental Program have been performed. The interviews with the professionals aimed at understanding their point of view concerning the infantile accidents. The data analysis was based on four determinants: the accident as a casual event, the accident as a consequence of the carelessness or negligence of the adult responsible for the children, the accident as the manifestation of the physical violence against the child, and the accident as a depressive profile of the child. The findings allowed us to associate the accidents to psychological, sex, biological and social factors. Many times the accident have contributed to hide the depression, the negligence, and the violence against the child, assuming different meanings... (Complete abstract, click electronic access below) / Mestre

La perpétuation de l'islam sénégalais repose en grande partie sur l'enseignement musulman, traditionnellement réalisé dans des écoles coraniques (daara) par des maîtres reconnus pour leurs compétences religieuses. Des enfants leur sont confiés par leur famille, souvent pauvre en milieu rural. Une partie de ces écoles migre pour s'installer en ville, suite à divers bouleversements socio-économiques subis par le Sénégal depuis une quarantaine d'années. Certains de ces élèves deviennent alors des taalibe-mendiants : la quête majoritairement monétaire qu'ils pratiquent et les rapports entretenus avec leur maître sont basés sur des principes culturels et cultuels anciens, ayant muté depuis quelques décennies. L'élève coranique se situe au centre de différentes sortes d'échanges de prestations et de dons sur fond de baraka (grâce divine). Ce travail de recherches se propose d'expliciter les stratégies élaborées par les multiples acteurs sociaux – maîtres, chefs religieux, parents, population donnant l'aumône (sarax) suite à l'injonction d'un marabout devin/guérisseur…– interagissant dans ce phénomène, afin de comprendre les changements problématiques subis par ce type d'enseignement. L'utilisation de la théorie du don initiée par Mauss permet d'analyser l'évolution de la fonction sociale du taalibe-mendiant, qui ne doit pas être confondu avec un faxman (enfant des rues), présent lui aussi au Sénégal. / The perpetuation of Senegalese Islam is based in major part on Muslim teaching, traditionally fulfilled in Koranic schools (daara) by masters acknowledged for their religious skills. Children are entrusted to them by their families, often poor in rural environments. A certain amount of these schools migrate to settle in the city, due to various socio-economic changes experienced by Senegal in the last forty years. Some of these students then become taalibe-beggars: the quest mostly monetary they practice and the relationships maintained with their masters are based on ancient cultural and religious principles having mutated in recent decades. The Koranic student is at the center of various kinds of service and gift exchanges based on the baraka (divine grace) principle. This research aims to explain the different strategies developed by the multiple social actors – teachers, religious leaders, parents, people giving alms (sarax) following the injunction of a marabout diviner/healer ... – interacting in this phenomenon, so as to understand the problematic changes went thought by this type of teaching. The gift theory thought out by Mauss permit to analyze the taalibe-beggar social functions' evolution, which should not be confused with a faxman (children of the streets), also present in Senegal.

published_or_final_version / Microbiology / Doctoral / Doctor of Philosophy

Infantile nystagmus is a condition that causes involuntary, bilateral and conjugate oscillations of the eyes, which are predominately restricted to the horizontal plane. In order to investigate the cause of nystagmus, computational models and nonlinear dynamics techniques have been used to model and analyse the oculomotor system. Computational models are important in making predictions and creating a quantitative framework for the analysis of the oculomotor system. Parameter estimation is a critical step in the construction and analysis of these models. A preliminary parameter estimation of a nonlinear dynamics model proposed by Broomhead et al. [1] has been shown to be able to simulate both normal rapid eye movements (i.e. saccades) and nystagmus oscillations. The application of nonlinear analysis to experimental jerk nystagmus recordings, has shown that the local dimensions number of the oscillation varies across the phase angle of the nystagmus cycle. It has been hypothesised that this is due to the impact of signal dependent noise (SDN) on the neural commands in the oculomotor system. The main aims of this study were: (i) to develop parameter estimation methods for the Broomhead et al. [1] model in order to explore its predictive capacity by fitting it to experimental recordings of nystagmus waveforms and saccades; (ii) to develop a stochastic oculomotor model and examine the hypothesis that noise on the neural commands could be the cause of the behavioural characteristics measured from experimental nystagmus time series using nonlinear analysis techniques. In this work, two parameter estimation methods were developed, one for fitting the model to the experimental nystagmus waveforms and one to saccades. By using the former method, we successfully fitted the model to experimental nystagmus waveforms. This fit allowed to find the specific parameter values that set the model to generate these waveforms. The types of the waveforms that we successfully fitted were asymmetric pseudo-cycloid, jerk and jerk with extended foveation. The fit of other types of nystagmus waveforms were not examined in this work. Moreover, the results showed which waveforms the model can generate almost perfectly and the waveform characteristics of a number of jerk waveforms which it cannot exactly generate. These characteristics were on a specific type of jerk nystagmus waveforms with a very extreme fast phase. The latter parameter estimation method allowed us to explore whether the model can generate horizontal saccades of different amplitudes with the same behaviour as observed experimentally. The results suggest that the model can generate the experimental saccadic velocity profiles of different saccadic amplitudes. However, the results show that best fittings of the model to the experimental data are when different model parameter values were used for different saccadic amplitude. Our parameter estimation methods are based on multi-objective genetic algorithms (MOGA), which have the advantage of optimising biological models with a multi-objective, high-dimensional and complex search space. However, the integration of these models, for a wide range of parameter combinations, is very computationally intensive for a single central processing unit (CPU). To overcome this obstacle, we accelerated the parameter estimation method by utilising the parallel capabilities of a graphics processing unit (GPU). Depending of the GPU model, this could provide a speedup of 30 compared to a midrange CPU. The stochastic model that we developed is based on the Broomhead et al. [1] model, with signal dependent noise (SDN) and constant noise (CN) added to the neural commands. We fitted the stochastic model to saccades and jerk nystagmus waveforms. It was found that SDN and CN can cause similar variability to the local dimensions number of the oscillation as found in the experimental jerk nystagmus waveforms and in the case of saccade generation the saccadic variability recorded experimentally. However, there are small differences in the simulated behaviour compared to the nystagmus experimental data. We hypothesise that these could be caused by the inability of the model to simulate exactly key jerk waveform characteristics. Moreover, the differences between the simulations and the experimental nystagmus waveforms indicate that the proposed model requires further expansion, and this could include other oculomotor subsystem(s).

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

L’année de son ouverture (1802 – 1803), l’hôpital des Enfants malades de Paris, premier hôpital pour enfants au monde, accueille 2229 enfants (avec 300 lits), le taux de mortalité est de 21,5% ; les années suivantes, il est plutôt de l’ordre de 25%. Au début du siècle (1802-1810), la durée moyenne d’hospitalisation est supérieure à 80 jours, les dépenses annuelles sont de l’ordre de 200 000 francs et le coût d’un lit d’hospitalisation est d’environ 500 francs. Plus d’un siècle après, en 1913, l’hôpital des Enfants malades admet 8945 (600 lits) enfants, soit 5 fois plus qu’en 1802 – 1803, alors qu’il n’est plus le seul hôpital pédiatrique de Paris (s’y ajoutent Trousseau en 1854, Hérold et Bretonneau en 1901). La mortalité n’est plus que de 13.74%, soit à peu près la moitié de celle du début du siècle, une diminution significative certes, mais un chiffre encore élevé qui est cependant à nuancer par l’hospitalisation dès les années 1880 des nourrissons (enfants de moins de 2 ans dont la mortalité est très importante et qui n’étaient pas accueillis auparavant). La durée d’hospitalisation chute (en moyenne 23 jours), les dépenses explosent : 1 400 000 francs en 1913, et chaque lit d’hospitalisation coûte 2200 francs.La création de l’hôpital des Enfants malades permet aux enfants de ne plus être mélangés à des adultes qui avaient une influence néfaste. Il assure une meilleure observation des maladies infantiles et un traitement plus approprié. De grands médecins y exercent (Guersant, Trousseau, Roger, Grancher, Variot, Marfan, Hutinel), ils mettent en place de nouveaux traitements (curatifs et préventifs) et font progresser la médecine infantile. L’évolution des mentalités et les avancées scientifiques favorisent la mutation de l’hôpital pour enfants : transformation des lieux d’hospitalisation, création de laboratoires et de bibliothèques, augmentation et nouvelles priorités du budget, amélioration des conditions de travail et de la formation des personnels de soins, laïcisation de l’hôpital.La population infantile admise aux Enfants malades appartient à la classe la plus pauvre, malade, mal nourrie et mal vêtue ; l’institution essaie de les sauver. Ces enfants sont la plupart du temps atteint de maladies infectieuses, l’étude de la variole, de la scrofule, du choléra, de la diphtérie et des gastroentérites illustre les pathologies infantiles du XIXe siècle, ainsi que l’évolution de leur pris en charge. Administration (argent), médecins (science) et familles (confiance) ont eu un rôle essentiel dans le développement de l’hospitalisation. Ainsi, passe-t-on des soins maternels à la pédiatrie. / The hospital “les Enfants malades” of Paris was opened in May 1802; it was the first children’s hospital in the world. The first year, it accommodated 2,229 children (with 300 beds), and the death rate was 21, 5%. The next years it was around 25%. At the turn of the century (1802-1810), the average time of hospitalization was more than 80 days, and yearly expenses were around 200,000 francs. A hospital bed cost about 500 francs. A century later, in 1913, the hospital “les Enfants malades” of Paris admitted 8,945 children (with 600 beds), that is to say five times more than the period 1802-1803. Yet other children’s hospitals were built: Trousseau in 1854, Hérold and Bretonneau in 1901. The death rate was 13, 74%, half that of the beginning of the century. This was a significant reduction, but this figure was still too high. Before 1880 children below the age of two years were not admitted to the hospital. The death rate amongst this age group was considerable. After 1880 all children up to the age of fifteen were admitted. The hospitalization time fell (around 23 days), the expenses rose steeply: 1,400,000 francs in 1913 and each hospital bed cost 2,200 francs.The foundation of the hospital “les Enfants malades” of Paris allowed children to be treated separately from the adults. Treating children separately from adults was good for their emotional wellbeing. Better observation of infantile diseases and appropriate treatment were given thanks to this institution. Great doctors (Guersant, Trousseau, Roger, Grancher, Variot, Marfan, Hutinel) practiced and developed new treatments, both curative and preventive, and made great progress in infantile medicine. New ways of thinking about children and the advancement of science facilitated the hospital’s change: transformation of hospital wards, the creation of laboratories and libraries, additional funding, improvement of working conditions and nurses’ training schools, and the separation of the church and state.The population of hospital les “Enfants malades” appertained to the poorer classes, sick, ill-fed, and ill-clothed children. The institution tried to save them. In 19th century, the main infantile diseases were infectious diseases. The study of smallpox, scrofula, cholera, diphtheria and gastro-enteritis were the main conditions treated throughout the century. Administration (money), physicians (science) and families (confidence) have had a fundamental part in the evolution of children’s hospitalization. So, it passed from maternal care to include pediatrics

Des mutations du gène ARX (aristaless-related homeobox gene) ont été identifiées dans un large spectre de désordres neurologiques précoces, incluant ou non des malformations cérébrales, le plus souvent associés à des épilepsies. Il est proposé que le gène ARX, codant pour un facteur de transcription, joue un rôle primordial au cours du développement cérébral, notamment sur la migration des neurones GABAergiques, mais son implication au cours de la mise en place du système nerveux central reste cependant encore mal connue. L’objectif de ce travail a été d’étudier le rôle du gène ARX et les conséquences de ses mutations sur le développement cérébral dans le but de mieux comprendre ces pathologies. Dans un premier temps, nous avons étudié l’effet d’une mutation particulière du gène, la mutation ARX(CGC)7, une expansion polyalanine retrouvée principalement dans des pathologies sans malformation cérébrale mais avec des épilepsies, tels que les syndromes de West ou d’Ohtahara. Des analyses réalisées sur une lignée de souris knock-in pour cette mutation (GCG)7 et sur des rats après électroporation in utero ont montré que la migration neuronale des neurones glutamatergiques et GABAergiques ainsi que la maturation des neurones GABAergiques ne sont pas altérées par cette mutation. De façon intéressante, nos données suggèrent que les épilepsies observées chez les souris knock-in résulteraient plutôt d’une réorganisation du réseau glutamatergique. Etant donné que le gène ARX n’est pas exprimé dans les neurones glutamatergiques, l’ensemble de ce travail suggère donc que les épilepsies chez les souris knock-in pour la mutation (GCG)7 sont la conséquence d’une altération développementale secondaire à la mutation initiale du gène, et ceci aurait d’importantes répercussions thérapeutiques qui requièrent d’avantages d’études. Des expériences nous ont ensuite permis d’étudier l’effet de plusieurs mutations du gène ARX sur la morphologie des interneurones in vitro. Celles-ci ont montré que les mutations d’ARX n’engendrent pas une localisation subcellulaire anormale de la protéine dans les interneurones en culture. De façon intéressante, ces expériences suggèrent que la morphologie des interneurones est altérée seulement par certaines mutations, notamment les mutations P353R et Dup24. Ces données soulignent ainsi l’importance d’étudier de façon spécifique chaque mutation du gène pour expliquer les mécanismes engendrant l’hétérogénéité phénotypique liée aux mutations d’ARX. L’ensemble de ces travaux contribuent à une meilleure compréhension du rôle du gène ARX dans le développement cortical et à une meilleure caractérisation des mécanismes physiopathologiques des désordres neurologiques précoces liés aux mutations de ce gène. / Several mutations in ARX gene (aristaless-related homeobox gene) have been found in a large spectrum of infantile neurological disorders, with or without cerebral malformation, but frequently linked to epilepsy. It has been proposed that ARX, coding for a transcription factor, plays a crucial role in brain development, especially in migrating interneurons, but its involvement in nervous system development still remains to be clarified. The aim of this work has been to study the role of ARX gene and the consequences of ARX mutations on cerebral development in order to better understand these pathologies.We have first investigated the effects of an ARX polyalanine expansion, the mutation (GCG)7, which was found in pathologies without brain malformation but associated to epilepsy, such as West and Ohtahara syndromes. Analysis performed on knock-in mice for this mutation and in utero electroporated rat brains have shown that this mutation doesn’t alter neither glutamatergic and GABAergic neuronal migration, nor GABAergic neuron maturation. Interestingly, our data suggest that epilepsy observed in knock-in mice would result rather from a reorganization of glutamatergic networks. Since ARX gene is not expressed in excitatory neurons, our work suggests that epilepsy observed in knock-in mice is the consequence of developmental alterations secondary to the initial mutation, and this would have crucial therapeutic implications that require additional investigations. In vitro experiments have then allowed us to study the effect of several ARX mutations on interneurons morphology. These experiments have shown no abnormal subcellular localization of ARX protein following transfection of these different mutations in cultured interneurons. Interestingly, our data show that interneuron morphology is altered only by some mutations, particularly the P353R and the Dup24 ARX mutations. Our data underline the importance to study specifically each mutation in order to explain mechanisms generating phenotypic heterogeneity linked to ARX mutations.Taken together, this study contributes to a better understanding of ARX involvement in cerebral development and to a better characterization of pathophysiological mechanisms linked to ARX mutations.