Processor design has evolved over the years to take advantage of new technology and innovative concepts in order to improve performance. Diminishing returns for improvements based on current techniques such as exploiting instruction-level parallelism have caused designers to shift their focus. Rather then focusing on single-threaded architectures, designers have increasingly sought to improve system performance and increase overall throughput by exploiting thread-level parallelism through multithreaded multi-core architectures. Software modeling and simulation are common techniques used to aid hardware design. Through simulation, different architectures can be explored and verified before hardware is actually built. An appropriate choice for the level of abstraction can reduce the complexity and the time required to create and simulate software models. The first contribution of this thesis is a transaction-level simulation model of a multithreaded multi-core processor. The transaction level is a high level of abstraction that hides computational details from the designer allowing key architectural elements to be quickly explored. The processor model that has been implemented for this thesis is flexible and can be used to explore various designs by simulating different processor and cache configurations. The processor model is written in SystemC, which is a standard design and verification language that is built on C++ and that can be used to model hardware systems. The second contribution of this thesis is the development of an application model that seeks to characterize the behavior of instruction execution and data accesses in a program. An application's instruction trace can be profiled to produce a model that can be used to generate a synthetic trace with similar characteristics. The synthetic trace can then be used in place of large trace files to drive the SystemC-based processor model. The application model can also produce various workload scenarios for multiprocessor simulation. From experimentation, various processor configurations and different workload scenarios were simulated to explore the potential benefits of a multi-core multithreaded processor architecture. Performance increased with diminishing returns with additional multi-core multithreading support. However, these improvement were limited by the utilization of the shared bus. / Thesis (Master, Electrical & Computer Engineering) -- Queen's University, 2007-08-09 11:45:46.749

La maladie de Charcot-Marie-Tooth de type 4H est une neuropathie héréditaire sensitivo-motrice démyélinisante à transmission récessive. Elle est causée par à des mutations dans le gène FGD4 codant la protéine FRABIN, RhoGEF comportant cinq domaines fonctionnels : un domaine FAB de liaison à l’actine, un domaine DH à activité d’échange GDP/GTP sur les petites RhoGTPases, deux domaines PH et un domaine FYVE impliqués tous trois dans la liaison aux polyphosphoinositides. D’une part, nous avons pu identifier trois nouvelles mutations, portant à dix le nombre de mutations dans FGD4. D’autre part, des études transcriptionnelles ont permis de caractériser huit transcrits alternatifs pouvant coder pour différentes isoformes de FRABIN, dépourvues de différents domaines. Ces résultats suggèrent que FRABIN pourrait être une protéine modulaire. J’ai pu montrer que, dans les fibroblastes des patients, la protéine FRABIN était absente. Dans les lymphoblastes, nous supposons que l’isoforme FRABIN présente est dépourvue du domaine de liaison à l’actine, mais nous n’avons pas pu analyser l’effet des mutations sur la production de la protéine. Dans les fibroblastes et les lignées lymphoblastoïdes des patients, j’ai pu mettre en évidence une diminution drastique de l’activation des RhoGTPases CDC42 et RAC1. Cependant, cette diminution n’a pas pu être corrélée avec des anomalies du cytosquelette ou de la migration des fibroblastes des patients. Toutefois, ces RhoGTPases sont primordiales pour la myélinisation, il est donc fort possible que dans les cellules du système nerveux périphérique, la perte de FRABIN résultant en une diminution de plus de 50% de l’activation des RhoGTPases entraîne des défauts majeurs dans le processus de « radial sorting ». L’arrivée des souris KO conditionnelles pour fgd4 dans les cellules de Schwann ou dans les motoneurones, devrait nous permettre de valider ou d’infirmer plusieurs hypothèses qui ont été émises durant ce travail et ainsi de mieux comprendre la physiopathologie de la maladie. / CMT4H is an autosomal recessive demyelinating CMT due to mutations in FGD4, which encodes FRABIN. FRABIN has five functional domains: a F-actin binding domain, a RhoGEF domain with GDP/GTP exchange activity, two PH and one FYVE domains which interact with polyphosphoinositides. In this study, we identified three novel FGD4 mutations, bringing to ten the number of mutations in this gene. Moreover, I characterized eight alternative transcripts, and all of them could lead to a functional FRABIN isoform, deprived of one or more functional domains. This led us to consider FRABIN as a modular protein. In patient’s fibroblasts, I have been able to show that FRABIN is degraded. Unlike in patient’s lymphoblastoïd cells line where we were unable to characterize the mutation effect on the protein. In these cells, we proposed that FRABIN is present without the F actin binding domain. Nevertheless, in patient’s fibroblasts and lymphoblastoïde cells line, I showed a major diminution of the CDC42 and RAC1 active forms, which is not in correlation with the absence of abnormalities in cytoskeleton and migration of patient‘s fibroblasts. We suggested that, in peripheral nerve system cells, the diminution of these RhoGTPases activation is damaging for the myelination. We are waiting for two fgd4 conditional KO mice model (one in Schwann cells and one in neuron). Exploration of these models will allow us to explain the physiopathological mechanism of CMT4H.

La maladie de Charcot-Marie-Tooth représente un groupe hétérogène de maladies tant sur le plan clinique que sur le plan génétique. A ce jour, on dénombre 60 gènes décrits dans la maladie de CMT. En Tunisie, le fort taux de consanguinité est un facteur majeur de l'apparition des maladies génétiques en particulier des formes autosomiques récessives parmi lesquelles, on trouve la maladie de Charcot-Marie-Tooth. Deux formes de CMT ont été identifiées dans cette population, il s'agit de la forme CMT4A et la forme de CMT4B2. Mes travaux de thèse ont consisté à identifier de nouveaux gènes chez des familles tunisiennes consanguines atteintes de CMT en utilisant différentes approches de criblages. J'ai poursuivi aussi des travaux de localisation réalisées chez deux familles libanaises consanguines et pour lesquelles les analyses n'ont pas permis d'identifier une région homozygote par descendance. Nous avons pu caractériser les formes CMT4H, CMT4C et CMT1A dans la population tunisienne. Nous avons identifié une nouvelle mutation dans le gène FGD4 impliquée dans la forme CMT4H. Nous avons pu caractériser la forme CMT4C par l'identification d'une nouvelle mutation dans le gène SH3TC2. En utilisant la technique d'hybridation génomique comparative sur des puces CGH , le criblage nous a permis de mettre en évidence la forme dominante CMT1A chez des patients tunisiens. / My research is entitled "Molecular analysis of consanguineous families Tunisian and Lebanese with clinical signs of Charcot-Marie-Tooth disease". The objectives of the PhD research were to identify and localize the genes implicated in these clinic forms of CMT and to elucidate the functional impact of mutations and the associated physiopathology mechanisms. For this purpose several technologies were used such as Fluorescent Direct Sequencing of known genes published in CMT disease. We have identified two novel mutations in patients from consanguineous Tunisian families: the first mutation (c.514_514insG; p.Ala172Glyfs*27) was detected in FGD4 by Fluorescent direct sequencing. Skin and nerve biopsy structure of these patients were studied under a microscope. Furthermore, the expression profile of FRABIN was studied by western blot. The cellular localization of this protein is under further examinations with the use of immunofluorescent. The second mutation (c.2968delC; p.Leu990Trpfs*24) was identified using High throughput sequencing in the SH3TC2 gene, The duplication of CMT1A in patients from Tunisia was demonstrated by Array CGH technique. The identified mutations will be subjected to functional studies to determine their impact on protein and to investigate the pathophysiology of this disease. Detail data analysis is currently underway for these projects using High throughput sequencing and other methods as appropriate in both Tunisian and Lebanese families.

The diploma thesis titled "Quality assessment by non-destructive technologies" is focused at evaluation degradation qualities of welded components, which are material heterogeneous. Welded samples are made for experimental measuring by CMT method and their degradation qualities are measured by the acoustic emission during the corrosion process and tensile straining. The theoretical part is aimed at on basic division most used method NDT, the main stress is on AE. Te final part is focused on corrosion engineering, especially on problematic galvanic corrosion, which is important in case of interaction of homogenous materials. Material samples which were used are mentioned at the beginning of experimental part. Then the thesis is dedicated to summary of methods used during the measurement. The next chapter provides courses and exp. results of observations and measurements using AE. Courses and exp. results of observations and measurements using AE are in the last chapter.

The mitofusin 1 and 2 (MFN and MFN2) proteins reside in the outer mitochondrial membrane and have been shown to regulate mitochondrial network architecture by mediating tethering and fusion of mitochondria. Mitochondria normally form a tubular and branched reticular network dynamically regulated by a balance of fusion and fission events. Absence of either Mfn1 or Mfn2 results in a fragmented mitochondrial network. Züchner et al. previously described mutations in the gene mitofusin 2 (MFN2) as the cause of the major autosomal-dominant, axonal form of Charcot-Marie-Tooth neuropathy (CMT2A). CMT type 2 (CMT2) is characterized by chronic axonal degeneration of peripheral nerves leading to the loss of functional nerve fibers. Mutations in MFN2 are the most common cause of CMT2, and in Chapter 2 we report the results from a genetic screen of MFN2 in a CMT2 patient cohort. The original finding that mutations in MFN2 cause CMT2A led to investigations focused on deficiencies of mitochondrial fusion and transport, specifically in the context of long axonal processes affected in CMT. While some experimental work supports disrupted mitochondrial transport in the etiology of CMT2A, other studies on CMT2A patient fibroblasts and cell models suggest abnormal mitochondrial fusion and dynamics do not underlie the etiology of this. In the first half of Chapter 3, we present some of our initial investigations prior to de Brito and Scorrano’s report published in 2008 regarding a novel role for Mfn2 in tethering the endoplasmic reticulum (ER) to mitochondria. In Mfn2 null mouse embryonic fibroblasts (MEFs) regions of contact between mitochondria and the endoplasmic reticulum (ER) are significantly reduced. These regions of contact are thought to form specialized subdomains of the ER, called mitochondrial associated membranes (MAM). Besides observing a fragmented ER network in Mfn2 knockout (KO) mouse embryonic (MEF) cells, de Brito and Scorrano presented several lines of evidence which suggest that the underlying pathogenic mechanism in CMT2A stems from disrupted ER-mitochondria. As this observation had not been replicated in the literature, we describe our attempts to replicate these finding in the last half of Chapter 3. The MAM represents a sub-domain of the ER in close association with the mitochondrial outer membrane. The movement of phosphatidylserine (PS) from the MAM domains of the ER to mitochondria and its subsequent decarboxylation to phosphatidylethanolamine (PE) by the enzyme PS decarboxylase (Pisd) has been well characterized and is known to depend on the existence of an outer mitochondrial membrane protein. As PE has curvature inducing and fusogenic biophysical characteristics, a deficiency in PE would be an attractive mechanism contributing to the morphological and fusion defects observed in Mfn2 null cell models. We hypothesized that loss of Mfn2 would lead to specific decreases in mitochondrial and cellular levels of PE. Chapter 4 describes experiments designed to test this hypothesis. We observed significantly lower levels of PE in Mfn2 null cells, yet observe similar changes in Mfn1 null cells. Likewise, other lipid species such as ether linked PE (ePE) are decreased. To investigate how CMT2A mutations in MFN2 influence cellular phospholipid profiles, we then profiled cellular phospholipids of CMT2A patients and control lymphoblasts. We hypothesized that mutations in MFN2 would result in decreased levels of PE. In Chapter 5, we report the results of a phospholipid screen which reveal changes in ePE in CMT2A patient lymphoblasts, without the drastic decreases in PE previously observed in Mfn2 null lines. In conclusion, our data indicates an important role for both mitofusins in the mitochondrial synthesis of PE. In the context of CMT2A mutations, ePE levels are specifically reduced. Future studies may reveal how deficiencies in ePE might have important functional consequences in the pathogenesis of CMT2A.

Context: The data transmission mechanisms in a multi-homed network has gained importance in the past few years because of its potentials. Concurrent multipath transmission (CMT) technique uses the available network interfaces for transmission by pooling multiple paths together. It allows transport mechanisms to work independent of the underlying technology, which resembles the concept of Transport Virtualization (TV). As a result, in the development of Future Internet Architectures (FIA), TV plays a vital role. The leading commercial software technologies like IOS and Android have implemented such mechanisms in their devices. Multipath TCP and CMT-SCTP are the protocols under development which support this feature. The implementation and evaluation of CMT in real-time is complex because of the challenges like path binding, out-of-order packet delivery, packet-reordering and end-to-end delay. Objectives: The main objective of this thesis is to identify the possibilities of implementing CMT in real-time using multiple access technologies, and to evaluate the performance of transmission by measurements and analysis under different scenarios. Methods: To fulfill the objectives of the thesis, different methods are adopted. The development of CMT scenario is based on a spiral methodology where each spiral refers to different objectives. The sub-stages in a spiral are mainly implementation, observations, decisions and modifications. In order to implement and identify the possibilities of CMT in real-time, a deep literature study is performed beforehand. Results: The throughput of data transmission is less affected by varying the total number of TCP connections in transmission. Under different cases it is observed that the throughput has significant impact by varying number of efficient paths in transmission. Conclusion: From the experimental methodology of this work it can be observed that, CMT can be implemented in real-time using off-the-shelf components. Based on the experimentation results, it can be concluded that the throughput of transmission is affected by increasing number of paths. It can also be concluded that the total number of TCP connections during the transmission have less impact on throughput.

O elevado custo dos tratamentos tradicionais da mastite bovina, associado à redução de produção e inviabilidade de tratamento das mastites subclínicas durante a lactação, bem como a exigência cada vez mais rigorosa da ausência de resíduos de antimicrobianos por parte de instituições nacionais e internacionais, impulsiona o desenvolvimento de novas alternativas terapêuticas que visem minimizar o impacto das medidas tradicionais de tratamento. A homeopatia surge como importante alternativa, sendo aceita nacional e internacionalmente. O objetivo do trabalho foi avaliar o tratamento homeopático com Phytolacca decandra 30CH durante a lactação de vacas com mastite subclínica, utilizando parâmetros de qualidade do leite como Califórnia Mastitis Test (CMT), contagem de células somáticas (CCS) totais, porcentagens de polimorfonucleares (PMN) e de mononucleares (MN), teores de proteína, lactose, gordura, sólidos totais (ST) e extrato seco desengordurado (ESD), além da mensuração da produção leiteira. Foram selecionadas 26 vacas, CMT 2+ e 3+ sem sinais de mastite clínica, entre o terceiro e sexto mês de lactação, pluríparas e divididas em dois grupos, um com tratamentos medicamentosos mensais e outro com tratamentos quinzenais. Mensalmente foram colhidas duas amostras de leite de cada glândula mamária (teto) que apresentava mastite subclínica. Uma das amostras foi utilizada para CCS e análise dos componentes do leite, e a outra para identificação microbiológica. Nos grupos tratados, foi administrado o medicamento homeopático Phytolaca decandra 30CH diluído em água e aspergido nas mucosas oro-nasais e vaginais, enquanto que nos grupos denominados controle foi administrado placebo da mesma maneira. A pesagem da produção láctea de ambos os grupos foi realizada quinzenalmente até o final do experimento. Verificou-se então que não houve diferença significativa entre a produção láctea, CCS e a presença de microrganismos na secreção láctea das glândulas quando comparadas antes e depois do tratamento homeopático, dentro de cada grupo, bem como quando comparados os grupos entre si. As medianas de CMT e porcentagens de PMN foram compatíveis com infecções mamárias agudas, embora os animais tenham sido diagnosticados como portadores de mastites crônicas e em nenhum momento desenvolveram sinais clínicos. / The high cost of traditional treatments of bovine mastitis, with the reduction of production and impracticable treatment of subclinical mastitis during lactation, as well as the requirement of an increased demand for absence of antimicrobial agents residues by national and international institutions, drives the development of new therapeutic alternatives in order to minimizing the impact of traditional treatment measures. The homeopathy appears as an important alternative, accepted domestically and internationally. The objective of this work was to evaluate homeopathic treatment with Phytolacca decandra 30CH during the lactation of cows with subclinical mastitis, using some milk quality parameters as California Mastitis Test (CMT), total somatic cell count (SCC), percentages of polymorphonuclear (PMN) and mononuclear (MN) cells, levels of protein, lactose, fat, total solids and dry defatted matter, in addition to the measurement of milk production. Twenty-six cows were selected with CMT 2 + and 3 + without any signs of clinical mastitis, between the third and sixth month of lactation, pluriparous and they were divided into two groups, with monthly or biweekly drug treatments. Monthly were collected two milk samples from each mammary gland (teat) that presented subclinical mastitis. One of the samples was used for analysis of SCC and milk components, and the other one for microbiological identification. In the treated groups, was given the homeopathic medicine Phytolaca decandra 30CH diluted in water and sprayed in the oral-nasal and vaginal mucosa, while to the control group was given placebo following the same method. The weighing of the milk production for both groups was performed fortnightly until the end of the experiment. There was no significant difference between milk production, SCC and the presence of microorganisms in milk gland secretion compared before and after homeopathic treatment, within each group as well as comparing the groups together. The medians of CMT and percentages of PMN were compatible with acute mammary infection, in spite of they have been diagnosed as carriers of chronic mastitis, and at any time no clinical signs have been developed.

O elevado custo dos tratamentos tradicionais da mastite bovina, associado à redução de produção e inviabilidade de tratamento das mastites subclínicas durante a lactação, bem como a exigência cada vez mais rigorosa da ausência de resíduos de antimicrobianos por parte de instituições nacionais e internacionais, impulsiona o desenvolvimento de novas alternativas terapêuticas que visem minimizar o impacto das medidas tradicionais de tratamento. A homeopatia surge como importante alternativa, sendo aceita nacional e internacionalmente. O objetivo do trabalho foi avaliar o tratamento homeopático com Phytolacca decandra 30CH durante a lactação de vacas com mastite subclínica, utilizando parâmetros de qualidade do leite como Califórnia Mastitis Test (CMT), contagem de células somáticas (CCS) totais, porcentagens de polimorfonucleares (PMN) e de mononucleares (MN), teores de proteína, lactose, gordura, sólidos totais (ST) e extrato seco desengordurado (ESD), além da mensuração da produção leiteira. Foram selecionadas 26 vacas, CMT 2+ e 3+ sem sinais de mastite clínica, entre o terceiro e sexto mês de lactação, pluríparas e divididas em dois grupos, um com tratamentos medicamentosos mensais e outro com tratamentos quinzenais. Mensalmente foram colhidas duas amostras de leite de cada glândula mamária (teto) que apresentava mastite subclínica. Uma das amostras foi utilizada para CCS e análise dos componentes do leite, e a outra para identificação microbiológica. Nos grupos tratados, foi administrado o medicamento homeopático Phytolaca decandra 30CH diluído em água e aspergido nas mucosas oro-nasais e vaginais, enquanto que nos grupos denominados controle foi administrado placebo da mesma maneira. A pesagem da produção láctea de ambos os grupos foi realizada quinzenalmente até o final do experimento. Verificou-se então que não houve diferença significativa entre a produção láctea, CCS e a presença de microrganismos na secreção láctea das glândulas quando comparadas antes e depois do tratamento homeopático, dentro de cada grupo, bem como quando comparados os grupos entre si. As medianas de CMT e porcentagens de PMN foram compatíveis com infecções mamárias agudas, embora os animais tenham sido diagnosticados como portadores de mastites crônicas e em nenhum momento desenvolveram sinais clínicos. / The high cost of traditional treatments of bovine mastitis, with the reduction of production and impracticable treatment of subclinical mastitis during lactation, as well as the requirement of an increased demand for absence of antimicrobial agents residues by national and international institutions, drives the development of new therapeutic alternatives in order to minimizing the impact of traditional treatment measures. The homeopathy appears as an important alternative, accepted domestically and internationally. The objective of this work was to evaluate homeopathic treatment with Phytolacca decandra 30CH during the lactation of cows with subclinical mastitis, using some milk quality parameters as California Mastitis Test (CMT), total somatic cell count (SCC), percentages of polymorphonuclear (PMN) and mononuclear (MN) cells, levels of protein, lactose, fat, total solids and dry defatted matter, in addition to the measurement of milk production. Twenty-six cows were selected with CMT 2 + and 3 + without any signs of clinical mastitis, between the third and sixth month of lactation, pluriparous and they were divided into two groups, with monthly or biweekly drug treatments. Monthly were collected two milk samples from each mammary gland (teat) that presented subclinical mastitis. One of the samples was used for analysis of SCC and milk components, and the other one for microbiological identification. In the treated groups, was given the homeopathic medicine Phytolaca decandra 30CH diluted in water and sprayed in the oral-nasal and vaginal mucosa, while to the control group was given placebo following the same method. The weighing of the milk production for both groups was performed fortnightly until the end of the experiment. There was no significant difference between milk production, SCC and the presence of microorganisms in milk gland secretion compared before and after homeopathic treatment, within each group as well as comparing the groups together. The medians of CMT and percentages of PMN were compatible with acute mammary infection, in spite of they have been diagnosed as carriers of chronic mastitis, and at any time no clinical signs have been developed.

Une méthode est proposée pour la modélisation d’unassemblage multimatériaux innovant visant des applicationsdans l’allègement structurel des véhicules. Dans cetassemblage une partie composite thermoplastique, est fixée àune plaque acier texturée par la technologie CMT pins.L’interface est particulièrement complexe et non linéaire : unereprésentation fine du comportement local serait extrêmementpénalisante en temps de calcul. Dans cette optique il a étéchoisi d’orienter la méthodologie vers une modélisation la plussimple possible tout en conservant de bons résultats globaux.Pour ce faire, en s’inspirant de l’état de l’art existant sur lesmultimatériaux, une campagne expérimentale a été menée surdes éprouvettes longitudinales à double recouvrement afin decaractériser cette interface. Une fois les mécanismes locauxinvestigués, deux modèles sont proposés. Le premiernumérique basé sur la méthode des éléments finis etl’introduction d’éléments cohésifs nous permet de valider leshypothèses de modélisation tout en quantifiant la répartitiondes efforts entre les picots. Le deuxième se base sur le calcullocal d’un Volume Élémentaire Représentatif pour établiranalytiquement la loi de comportement de l’interface. Cette loiest ensuite introduite sous la forme d’un ressort non linéaire ausein d’un modèle numérique simplifié de l’éprouvette. Pourfinir ces approches sont appliquées au cas d’étude industriel etles résultats sont validés par une deuxième campagneexpérimentale. / A method is proposed to simulate an innovative multimaterialassembly which has applications in structural lightweight forvehicles. In this assembly, a thermoplastic composite part isfixed on a steel plate, textured by the CMT pins technology.This is an especially complex and nonlinear interface: a finerepresentation of local behaviour would be extremely costlyfor calculation. So, it has been chosen to investigate a model assimple as possible which still demonstrates accurate globalresults.An experimental campaign on double lap shear specimen,inspired by existing state of the art on multimaterial has beenset up to characterize this interface. Once local mechanismshave been understood, two models are proposed and compared.The first is numerical and based on finite elements method andcohesive elements. It allows us to validate the modelhypotheses while describing the effort repartition between thepins. The second one is based on a Representative VolumeElement. It establishes analytically the behaviour law of theinterface. This law is then inserted inside a simplifiednumerical model of the specimen by means of a nonlinearspring. To conclude, these approaches are applied to theindustrial case of study and the result have been validated by asecond experimental campaign.

La maladie de Charcot-Marie-Tooth (CMT) est une pathologie neurologique affectant le système nerveux périphérique. Bien que décrite à la fin du XIXème siècle, la découverte d’une anomalie génétique n’a été identifiée chez ces patients que dans les années 1990 (duplication du gène PMP22). Depuis, de nombreux gènes ont été incriminés, et leur nombre ne cesse d’augmenter. Ainsi, cette multitude de gènes nous incite à rechercher des corrélations phénotype-génotype qui permettent d’orienter au mieux le diagnostic et la prise en charge de ces patients. Comme nous le montrons au travers de nos travaux, il est possible de s’appuyer sur des données cliniques, biologiques, électrophysiologiques (voire radiologiques) et histo-pathologiques (biopsie de nerf) pour orienter la recherche d’anomalies génétiques. Pour illustrer ceci, nous nous sommes appuyés sur l’exemple des mutations du gène INF2, gène récemment associé à la maladie de Charcot-Marie-Tooth. Dans ce cas précis, l’atteinte rénale, le profil électrophysiologique (forme « intermédiaire » de CMT) et surtout les données histo-pathologiques (la biopsie de nerf permettant de retrouver la présence d’expansions schwanniennes caractéristiques) sont évocatrices de la présence d’une anomalie portée par ce gène. D’autres exemples de corrélations génotype-phénotype sont apportés au travers d’observations. / Charcot-Marie-Tooth disease (CMT) is a neurological disorder of the peripheral nervous system. Even if it was described in the end of the nineteenth century, the first genetic abnormality (PMP22 duplication) was found only in the end of the twentieth century. Several other genes were found to be associated with this disease. This important number of potential genes leads us to find genotype-phenotype correlations in order to better and earlier diagnose these patients. As we can show it in our work, it is possible to use biological, electrophysiological (sometimes radiological) and pathological (nerve biopsy) in order to direct the genetic analysis towards the incriminated gene. To illustrate this, we have particularly study the INF2 gene, a gene recently associated with CMT. In this example, clinical (CMT phenotype and renal failure), electrophysiological (intermediate form of CMT), and pathological (supernumerary extensions of Schwann cells cytoplasm) features call to mind mutations in the INF2 gene. Other examples of genotype-phenotype correlations associated with various genes are reported in this manuscript.