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Les myopathies sont une maladie rare qui entraine une déficience musculaire. Il apparait que la plupart des myopathies présentent une modification dans la biodistribution et la concentration des collagènes. Le diagnostic actuel de ces maladies repose sur l’étude de protéines déficientes par des outils de biologie moléculaire dont les résultats sont incertains. Nous proposons de développer la spectro-imagerie IRTF pour différencier les cinq principaux types de collagène dans le tissu conjonctif musculaire. Pour cela, nous avons appliqué deux méthodes : la déconvolution spectrale de l’amide I et la détermination des coefficients d’extinction anisotropes des fibres. Nous avons ensuite mis au point une matrice synthétique mimant la composition moléculaire d’un tissu musculaire squelettique d’un muscle de bœuf. Cette matrice a pour but de calibrer la spectro-imagerie IRTF et de quantifier à moyen terme les collagènes dans les tissus. / Myopathies are a rare disease which leads a muscular deficiency. It seems that most of the myopathies present a modification in the biodistribution and in the concentration of collagens. The current diagnosis of these diseases is based on the study of deficient proteins by molecular biology techniques whose the results are uncertain. We suggest developing the spectro-imaging IRTF to differentiate five main types of collagen in the muscular connective tissue. For that, we applied two methods: the spectral déconvolution of the amide I and the determination of the anisotropic extinction coefficient of the fibers. Then, we have set up a synthetic matrix miming the molecular composition of a squeletic muscular tissue of beef muscle. This matrix aims at calibrating the spectro-imaging IRTTF and at quantifying in the medium term the collagen in tissues.

Procurou-se verificar a importância da miopatia exsudativa e despigmentada dentro das carnes suínas classificadas em nosso meio como insuficientes. Foram examinadas 87 amostras de lombo, pernil e paleta. A inspeção macroscópica das regiões nobres foi acompanhada da avaliação de algumas características físico-químicas além de exames histológicos nos músculos subscapularis, longissimus dorsi e massa muscular formada pela fusão dos músculos adductor e gracilis em amostras atingidas e não atingidas pela afecção. O estudo também se estendeu às áreas contíguas às lesões das amostras parcialmente afetadas. Verificou-se que as regiões atingidas da carcaça apresentaram lesões visíveis após o abate, observando-se áreas pálidas e exsudativas em 34.4 por cento dos lombos, 27,5 por cento dos pernis e 10,3 por cento das paletas. A afecção manifestou-se com maior intensidade nos lombos (20 por cento ) e pernis (12.5 por cento ). Nas paletas não foram observadas lesões acentuadas. Os exames laboratoriais confirmaram que as amostras provenientes de áreas atingidas apresentavam alterações características da miopatia exsudativa e despigmentada dos suínos. O pH das carnes afetadas, 45 minutos após o abate foi menor que o das carnes normais. Nas áreas atingidas, apesar dos valores para a umidade total permanecerem inalterados, houve maior perda de líquido das fibras musculares devido a diminuição do seu poder de retenção hídrico. Constatou-se, ademais, que nas áreas contíguas às lesões, apesar da musculatura ainda apresentar aparência macroscopica normal, as características físico-químicas e as estruturas histológicas já estavam modificadas com tendência a evidenciar as alterações típicas da afecção em estudo. As fibras musculares revelavam áreas acidófilas, desaparecimento das estriações e no caso das lesões graves as mesmas apresentavam-se fragmentadas. Esses dados permitiram-nos concluir que carcaças de suínos do tipo comum, usualmente destinados ao abate no Brasil, são passíveis de apresentarem lesões devidas à miopatia exsudativa e despigmentada. / The importance of the pale, soft and exudative muscle was studied in the pork considered insufficient in our country. Eighty-seven (87) samples of loin, ham and shoulder-blade were examined. The macroscopic inspection of these pieces was followed by some physico-chemical exams besides some histological exams in the subscapularis longissimus dorsi muscles and in the muscular portion formed by the adductor and gracilis muscles in affected and normal samples. The adjoining areas next to the injured ones were also studied. It was also verified that the affected regions in the carcasse presented visible damages after the slaughter by finding pale and exudative areas in 34,4 per cent of loins, 27,5 per cent of hams and 10,3 per cent of shoulder-blades. The affection was more intense in the loins (20 per cent ) and hams (12,5 per cent ). Bigger damages were not observed in the shoulder-blades. The laboratorial exams confirmed that the samples come from affected areas presented characteristic changes of the pale, soft and exudative muscle. Forty-five (45) minutes after the slaughter the pH of the watery pork was less than in the normal meat. Affected areas presented moisture content unaltered in spite of water holding capacity decreasing. It was also verified that in the adjoining areas the macroscopic appearance was still normal in spite of the physico-chemical characteristics and histological structures being modified with a tendency to show the typical changes of the affection. The muscular fibers showed acidophile areas, without striations and in the serious damages the fibers were broken. Through these data we may conclude that the carcasses of common swine, normally sent to slaughter in Brazil may present injuries because of the pale, soft and exudative condition.

Procurou-se verificar a importância da miopatia exsudativa e despigmentada dentro das carnes suínas classificadas em nosso meio como insuficientes. Foram examinadas 87 amostras de lombo, pernil e paleta. A inspeção macroscópica das regiões nobres foi acompanhada da avaliação de algumas características físico-químicas além de exames histológicos nos músculos subscapularis, longissimus dorsi e massa muscular formada pela fusão dos músculos adductor e gracilis em amostras atingidas e não atingidas pela afecção. O estudo também se estendeu às áreas contíguas às lesões das amostras parcialmente afetadas. Verificou-se que as regiões atingidas da carcaça apresentaram lesões visíveis após o abate, observando-se áreas pálidas e exsudativas em 34.4 por cento dos lombos, 27,5 por cento dos pernis e 10,3 por cento das paletas. A afecção manifestou-se com maior intensidade nos lombos (20 por cento ) e pernis (12.5 por cento ). Nas paletas não foram observadas lesões acentuadas. Os exames laboratoriais confirmaram que as amostras provenientes de áreas atingidas apresentavam alterações características da miopatia exsudativa e despigmentada dos suínos. O pH das carnes afetadas, 45 minutos após o abate foi menor que o das carnes normais. Nas áreas atingidas, apesar dos valores para a umidade total permanecerem inalterados, houve maior perda de líquido das fibras musculares devido a diminuição do seu poder de retenção hídrico. Constatou-se, ademais, que nas áreas contíguas às lesões, apesar da musculatura ainda apresentar aparência macroscopica normal, as características físico-químicas e as estruturas histológicas já estavam modificadas com tendência a evidenciar as alterações típicas da afecção em estudo. As fibras musculares revelavam áreas acidófilas, desaparecimento das estriações e no caso das lesões graves as mesmas apresentavam-se fragmentadas. Esses dados permitiram-nos concluir que carcaças de suínos do tipo comum, usualmente destinados ao abate no Brasil, são passíveis de apresentarem lesões devidas à miopatia exsudativa e despigmentada. / The importance of the pale, soft and exudative muscle was studied in the pork considered insufficient in our country. Eighty-seven (87) samples of loin, ham and shoulder-blade were examined. The macroscopic inspection of these pieces was followed by some physico-chemical exams besides some histological exams in the subscapularis longissimus dorsi muscles and in the muscular portion formed by the adductor and gracilis muscles in affected and normal samples. The adjoining areas next to the injured ones were also studied. It was also verified that the affected regions in the carcasse presented visible damages after the slaughter by finding pale and exudative areas in 34,4 per cent of loins, 27,5 per cent of hams and 10,3 per cent of shoulder-blades. The affection was more intense in the loins (20 per cent ) and hams (12,5 per cent ). Bigger damages were not observed in the shoulder-blades. The laboratorial exams confirmed that the samples come from affected areas presented characteristic changes of the pale, soft and exudative muscle. Forty-five (45) minutes after the slaughter the pH of the watery pork was less than in the normal meat. Affected areas presented moisture content unaltered in spite of water holding capacity decreasing. It was also verified that in the adjoining areas the macroscopic appearance was still normal in spite of the physico-chemical characteristics and histological structures being modified with a tendency to show the typical changes of the affection. The muscular fibers showed acidophile areas, without striations and in the serious damages the fibers were broken. Through these data we may conclude that the carcasses of common swine, normally sent to slaughter in Brazil may present injuries because of the pale, soft and exudative condition.

Submitted by CARINA GUIDI PINTO null (carina_guidi@hotmail.com) on 2016-02-26T12:56:51Z No. of bitstreams: 1 Dissertação Carina Guidi Pinto.pdf: 2764188 bytes, checksum: 30bbdd1a9fc0615c8dae9f321f8a83a1 (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-02-26T18:59:28Z (GMT) No. of bitstreams: 1 pinto_cg_me_bot.pdf: 2764188 bytes, checksum: 30bbdd1a9fc0615c8dae9f321f8a83a1 (MD5) / Made available in DSpace on 2016-02-26T18:59:28Z (GMT). No. of bitstreams: 1 pinto_cg_me_bot.pdf: 2764188 bytes, checksum: 30bbdd1a9fc0615c8dae9f321f8a83a1 (MD5) Previous issue date: 2016-01-22 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Pró-Reitoria de Pesquisa (PROPe UNESP) / A ingestão de etanol compromete a estrutura do cérebro, apresentar efeitos bifásicos sobre a atividade motora, agindo como um estimulante ou depressor dependendo da dose ou a duração de utilização. Ele interfere na absorção e metabolismo de vitamina D3, o que se correlaciona com alguns distúrbios neurológicos e neuropsiquiátricos. Há relatos sobre a associação de etanol com alterações ósseas, incluindo baixos níveis de vitamina D3. Com base nisso, o objetivo deste estudo foi avaliar os efeitos em testes de comportamento da administração isolada de vitamina D3 ou a sua administração em associação com etanol, durante alcoolismo crônico. A fim de conseguir isso, foram utilizados dois grupos experimentais: ratos Wistar machos (n = 20) e ratos UChB linhagem machos (n = 20) (bebedores voluntários de etanol). Ambos os grupos foram divididos em dois subgrupos: Vitamina D3 - 12.5μg / kg / dia (500 UI) de colecalciferol (WV, n = 10, e UV, n = 10), e de controle (CC, n = 10, e UC, n = 10), durante um período de 75 dias. O peso corporal análises e testes de comportamento (reflexo de sobressalto acústico e campo aberto) foram realizados em 90 e 165 dias de idade. Além disso, os níveis de plasma de corticosterona foram medidos a 165 dias, sem diferença estatística entre os grupos experimentais. O grupo Wistar apresentou valores mais baixos ASR no momento final (Controle e completada), enquanto as percentagens PPI foram maiores no grupo inicial. No grupo UChB houve nenhuma diferença em percentagens PPI com o pré-estímulos utilizados. Quando as respostas ASR foram comparados entre os grupos (Wistar e UChB), o grupo UChB apresentaram menores amplitudes de ASR quando comparados com os animais do grupo de ratos Wistar. Em relação à PPI percentagens dos três estímulos pré utilizados no grupo UChB, as percentagens foram maiores em comparação com os animais do grupo de ratos Wistar, os valores ASR foi menor no grupo UChB. A presença de fezes e urina foi semelhante tanto nos momentos iniciais e finais, no teste de campo aberto, para todos os grupos experimentais. Considerando-se os outros parâmetros de campo aberto, diminuição da locomoção foi observado no grupo UChB no subgrupo vitamina D3, bem como no grupo de controlo final, em comparação com o controlo inicial. Quando os grupos Wistar e UChB foram comparados, este último apresentado taxas mais elevadas na locomoção. Os resultados obtidos estão em consonância com o efeito sedativo / depressivo de etanol sobre o sistema nervoso central, reduzindo a ASR de amplitude, com um aumento provável ao longo dos circuitos inibitórios que medeiam a PPI, a determinação do aumento na percentagem de inibição no grupo UChB, bem como um aumento na locomoção apresentada pelo grupo UChB no teste de campo aberto, caracterizada por uma diminuição no efeito aversivo ao novo ambiente. Além disso ressaltamos que a dose de vitamina D3 usado não teve efeito sobre o parâmetro de comportamento analisados, diferenças observadas neste grupo parecendo estar relacionada a se acostumar com a sonda gástrica. Este estudo descreve pela primeira vez na literatura as diferenças nas respostas ao teste acústico de sobressalto reflexo entre ratos Wistar e UChB, este último geneticamente predispostos a ingestão de etanol, uma linhagem adequada para ser usada em experiências compreendendo análises de comportamento em face da ingestão de etanol. / Ethanol intake compromises brain structure, presenting biphasic effects over motor activity, acting as a stimulant or depressor depending on the dose or duration of use. It interferes in vitamin D3 absorption and metabolism, what correlates to some neurologic and neuropsychiatric disorders. There are reports on the association of ethanol with bone alterations, including low levels of vitamin D3. Based on that, the objective of this study was to evaluate the effects in behavior tests of isolated administration of vitamin D3 or its administration in association with ethanol, during chronic alcoholism. In order to achieve that, two experimental groups were used: male Wistar rats (n=20), and UChB lineage male rats (n=20) (volunteer ethanol drinkers). Both groups were divided in two subgroups: Vitamin D3 – 12.5µg/kg/day (500 UI) of cholecalciferol (WV, n=10, and UV, n=10), and Control (WC, n=10, and UC, n=10), for a period of 75 days. Body weight analyses and behavior tests (acoustic startle reflex and open field) were conducted at 90 and 165 days of age. In addition to that, corticosterone plasma levels were measured at 165 days, with no statistical difference between the experimental groups. The Wistar group presented lower ASR values in the final moment (Control and supplemented), while the PPI percentages were higher in the initial group. In the UChB group there was no difference in PPI percentages with the pre-stimuli used. When the ASR responses were compared between groups (Wistar and UChB), the UChB group presented lower ASR amplitudes as compared to the animals of the Wistar group. In relation to PPI percentages in the three pre stimuli used in the UChB group, the percentages were higher as compared to the animals in the Wistar group, the ASR values been smaller in the UChB group. The presence of feces and urine was similar both in the initial and final moments, in the open field test, for all the experimental groups. Considering the other parameters of open field, decreased locomotion was noted in the UChB group in the vitamin D3 subgroup, as well as in the final control group as compared to the initial control. When the Wistar and UChB groups were compared, the latter presented higher rates in locomotion. The results obtained are consonant to the depressive/sedative effect of ethanol over the CNS, reducing ASR amplitude, with a likely enhancement over the inhibitory circuits which mediate PPI, determining the increase in inhibition percentage in the UChB group, as well as an increase in locomotion presented by the UChB group in the open field test, characterized by a decrease in the aversive effect to the new environment. In addition we emphasize that the dose of vitamin D3 used did not have effect over the behavior parameter analyzed, differences observed in this group seeming to be related to getting used to the gavage. This study describes for the first time in literature the differences in responses to the acoustic startle reflex test between Wistar and UChB rats, the latter genetically predisposed to ethanol intake, a lineage adequate to be used in experiments comprising analyses of behavior in face of ethanol intake. / PROPe/RENOVE: 0252/010/14

Orientador: Selma Maria Michelin Matheus / Resumo: A ingestão de etanol compromete a estrutura do cérebro, apresentar efeitos bifásicos sobre a atividade motora, agindo como um estimulante ou depressor dependendo da dose ou a duração de utilização. Ele interfere na absorção e metabolismo de vitamina D3, o que se correlaciona com alguns distúrbios neurológicos e neuropsiquiátricos. Há relatos sobre a associação de etanol com alterações ósseas, incluindo baixos níveis de vitamina D3. Com base nisso, o objetivo deste estudo foi avaliar os efeitos em testes de comportamento da administração isolada de vitamina D3 ou a sua administração em associação com etanol, durante alcoolismo crônico. A fim de conseguir isso, foram utilizados dois grupos experimentais: ratos Wistar machos (n = 20) e ratos UChB linhagem machos (n = 20) (bebedores voluntários de etanol). Ambos os grupos foram divididos em dois subgrupos: Vitamina D3 - 12.5μg / kg / dia (500 UI) de colecalciferol (WV, n = 10, e UV, n = 10), e de controle (CC, n = 10, e UC, n = 10), durante um período de 75 dias. O peso corporal análises e testes de comportamento (reflexo de sobressalto acústico e campo aberto) foram realizados em 90 e 165 dias de idade. Além disso, os níveis de plasma de corticosterona foram medidos a 165 dias, sem diferença estatística entre os grupos experimentais. O grupo Wistar apresentou valores mais baixos ASR no momento final (Controle e completada), enquanto as percentagens PPI foram maiores no grupo inicial. No grupo UChB houve nenhuma diferença em perc... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Ethanol intake compromises brain structure, presenting biphasic effects over motor activity, acting as a stimulant or depressor depending on the dose or duration of use. It interferes in vitamin D3 absorption and metabolism, what correlates to some neurologic and neuropsychiatric disorders. There are reports on the association of ethanol with bone alterations, including low levels of vitamin D3. Based on that, the objective of this study was to evaluate the effects in behavior tests of isolated administration of vitamin D3 or its administration in association with ethanol, during chronic alcoholism. In order to achieve that, two experimental groups were used: male Wistar rats (n=20), and UChB lineage male rats (n=20) (volunteer ethanol drinkers). Both groups were divided in two subgroups: Vitamin D3 – 12.5µg/kg/day (500 UI) of cholecalciferol (WV, n=10, and UV, n=10), and Control (WC, n=10, and UC, n=10), for a period of 75 days. Body weight analyses and behavior tests (acoustic startle reflex and open field) were conducted at 90 and 165 days of age. In addition to that, corticosterone plasma levels were measured at 165 days, with no statistical difference between the experimental groups. The Wistar group presented lower ASR values in the final moment (Control and supplemented), while the PPI percentages were higher in the initial group. In the UChB group there was no difference in PPI percentages with the pre-stimuli used. When the ASR responses were compared between groups ... (Complete abstract click electronic access below) / Mestre

Background: The idiopathic inflammatory myopathies (IIM) are a heterogeneous group of rare autoimmune diseases comprising of polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM). They are characterised primarily by muscle weakness, and can present with extramuscular manifestations such as skin rashes, interstitial lung disease and malignancy. Aims: This aim of this study was to identify novel genetic risk factors in IIM and to further elucidate the relationship between genotype and serotype. Methods: 2,566 IIM samples were collected from 14 countries through the Myositis Genetics Consortium (MYOGEN) and genotyped on the Immunochip, a custom array covering 186 established autoimmune susceptibility loci. SNP2HLA was used to impute classical HLA alleles and constituent amino acids. Results: In a combined IIM analysis, the HLA region and PTPN22 reached genome-wide significance (p<5x10-8). A further nine regions reached suggestive significance (p<2.25x10-5) including UBE2L3, STAT4 and CD28 that have been implicated in autoimmune disease previously. Independent effects were seen within the STAT4 region. In a PM subgroup analysis (n=931), the HLA region and PTPN22 reached genome-wide significance. A further seven regions reached suggestive significance including SLC26A1/IDUA and RGS1. In an adult and juvenile DM analysis (n=1,360), only the HLA region reached genome wide significance. Three loci reached suggestive significance including GSDMB. In the IBM analysis (n=252), only the HLA region reached genome wide significance and 3 loci reached suggestive significance, including the CCR2 locus. Identification of exonic and eQTL SNPs has localised association signals to several potential causal variants. HLA imputation on the combined dataset confirmed that alleles of the 8.1 ancestral haplotype (AH) are most strongly associated with IIM. The cohort was stratified in to clinical subgroups. In PM the strongest effect was found with HLA-DRB1*03:01 with an independent effect with HLA-B*08:01. Amino acid position 74 lies within the peptide binding groove and may explain the risk in HLA-DRB1. HLA-B*08:01 was the most associated variant in both DM and JDM, with independent effects of amino acid position 57 of HLA-DQB1 in DM and HLA-C*02:02 in JDM. In IBM, the strongest associations were with amino acids positions 26 and 11 of HLA-DRB1.HLA imputation was conducted on antibody subgroups. The most associated variant for anti-Jo-1 and anti-PM/Scl antibodies was with amino acid 74 of HLA-DRB1. Alleles of the 8.1 AH were most associated with anti-TIF1-γ, anti-SAE and anti-cN1A antibodies. Alleles independent of the 8.1 AH were replicated such as anti-Mi-2 antibodies and HLA-DRB1*07:01, and anti-HMGCR antibodies and HLA-DRB1*11. Conclusions: This represents the largest study to date in IIM and has considerably expanded our knowledge about the genetic architecture of this rare disease. This study has identified novel disease susceptibility genes for IIM and independent associations with PM and DM, IBM and antibody subgroups that show that stratifying patients in to more homogenous cohorts is important to expand our knowledge of IIM. Ongoing sample collection is required to identify additional genes and environmental risk factors that lead to the development of IIM, and to expand our limited understanding of the pathogenesis of this disease.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Les myopathies congénitales sont des maladies neuromusculaires dont le diagnostic est établi grâce aux données cliniques, histologiques et génétique. Cependant, le diagnostic génétique est manquant pour la moitié des patients, ce qui suggère de nouveaux gènes impliqués. Le but de mon projet était d'identifier de nouveaux gènes de myopathies congénitales et de valider l'impact des mutations trouvées. En utilisant une stratégie d'analyse de séquençage d'exomes de patients déjà exclus pour les gènes connus, nous avons mis en évidence deux nouveaux gènes impliqués dans les myopathies congénitales. Des mutations récessives dans le gène PYROXD1, codant pour une oxydoréductase, causent une myopathie apparaissant à l'enfance avec des défauts spécifiques en histologie. Grâce à un modèle animal, nous avons montré que les mutations impactaient l'activité enzymatique de la protéine. Des mutations dominantes ou récessives dans le gène CACNA1S causent une myopathie avec un phénotype similaire pour toutes les mutations. Les études fonctionnelles ont montré que les mutations causaient un défaut dans le couplage excitation-contraction. / Congenital myopathies are neuromuscular diseases diagnosed by clinical, histological and genetic data. However, the genetic diagnosis is missing for half of the patients, suggesting new genes involved. The goal of my project was to identify new genes of congenital myopathies and validate the impact of the mutations. Using a strategy of analyzing DNA sequencing of patients already excluded for known genes, we have identified two new genes involved in congenital myopathies. Recessive mutations in the PYROXD1 gene, encoding an oxidoreductase, cause a myopathy with childhood-onset and a histology specific spectra. Functionnal studies showed that the mutations have an effect on the enzymatic activity of the protein. We showed that dominant or recessive mutations in the CACNA1S gene cause a neonatal onset myopathy with a similar phenotype for all found mutations.

Orientador: Anamarli Nucci / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-23T16:08:34Z (GMT). No. of bitstreams: 1 Rosa_TatianadaSilva_M.pdf: 1466384 bytes, checksum: 45b69dc792effba5fcc990ec7d2e1d65 (MD5) Previous issue date: 2013 / Resumo: As miopatias com centralização nuclear (MCM) são raras, heterogêneas quanto à clínica e genética e definidas pela histopatologia mostrando o núcleo central nas fibras musculares. Objetivos: avaliação fenotípica e funcional de pacientes com MCN, dando ênfase a métrica clínica, na serie de casos e individualmente. Métodos: O padrão ouro de diagnóstico foi a biópsia muscular. Fez-se revisão de 15 prontuários, e reavaliação clínica de 13 pacientes; aplicação das escalas medida da função motora, em português (MFM 32-P) e medida de independência funcional (MIF), exame de função pulmonar, goniometria e teste manual de força. Arbitrou-se escores individuais para a avaliação clínica, MFM 32-P, MIF e CVF% compondo um escore individual de gravidade. Usou-se estatística descritiva; e, o coeficiente de correlação de Pearson, com correção de Bonferroni, para investigar possíveis correlações, realizadas pelo programa SYSTAT v 9.0; nível de significância de 5%. Resultados: escores clínicos foram 3 (caso 4); 4 (caso 14); 7 (casos 8 e 10); 8 (caso 3); escore 9 (casos 5 e 15); 10 (caso 13); 12 (caso 11); 16 (casos 6 e 10); 17 (caso 7) e escore 18 (caso 9). A avaliação clinica diferenciou a MCN de inicio tardio daquelas de início precoce e congênitas, as primeiras com fenótipos de menor gravidade comparada com as últimas. Pela avaliação MFM 32-P obteve-se maior gravidade nos casos 6 a 10, quatro dos quais de início neonatal; casos 14 e 15, respectivamente, de início adulto e na adolescência. A MIF mostrou independência completa em 9/13 casos (69,2%); dois casos (15,3%) com dependência modificada de até 25% e outros dois com dependência de até 50%. A CVF<50% ocorreu em 5 casos (38,4%), CVF 50-69% em 6 casos (46,1%) e outros dois tiveram CVF>70%. Considerando o escore total individualizado de gravidade, o caso 7 obteve maior pontuação (24), sendo de forma neonatal e única cadeirante. Outros 23% tiveram escore igual ou acima de 20. MCN de gravidade intermediária (escores 11 a 15) foi observada em 53,8%; e 15,3% teve escore de 9 e 6, a menor gravidade. Essa se associou a inicio da MCN em adulto e em pacientes com longa duração da doença. Conclusão: Os instrumentos MFM 32-P e MIF permitiram caracterizar o espectro fenotípico da MCN e mostrar a variabilidade intrafamilial. Encontrou-se correlação positiva e significante entre a gravidade fenótipica motora detectada pela MFM 32-P e MIF em seus escores totais, assim como entre a D1 da MFM 32-P e os subdomínios mobilidade, locomoção e autocuidado da MIF. Não houve correlação entre a função pulmonar e as escalas MFM 32-P e MIF / Abstract: Myopathies with nuclear centralization are defined by histopathology. They are rare and heterogeneous in their clinical aspects and genetic. Objective: The study aimed to evaluate phenotypes in a cohort with centronuclear myopathies (CNM) and individual case, with emphasis on clinical and clinimetric. Methods:The gold standard for diagnosis was muscle biopsy. We reviewed medical records; patients were submitted to clinical examination, pulmonary function test, goniometry and manual test for strength (MRC). Scales measure of motor function, Portuguese version (MFM 32-P) and functional independence measure (FIM) were applied. Clinical evaluation, MFM 32-P, FIM and FVC% were arbitrarily scored and compose the sum for individual gravity score. Statistical analysis: we used descriptive statistic; and Pearson correlation coefficient with Bonferroni correction to investigate possible correlations in a SYSTAT v 9.0 program; significance level of 5%. Results: clinical scores were 3 (case 4); 4 (case 14); 7 (cases 8 and 10); 8 (case 3); score 9 (cases 5 and 15); 10 (case 13); 12 (case 11); 16 (cases 6 and 10), 17 (case 7), and score 18 (case 9). Clinical evaluation differentiates early onset CNM as more severe forms from adult onset CNM, the later with less scores. MFM 32-P showed higher severity in cases 6 to 10, four of which had neonatal onset CNM; cases 14 and 15 had adult-onset and adolescence expression, respectively. FIM showed complete independence in 9/13 cases (69.2%); two cases (15.3%) had modified dependence up to 25% and two with dependence up to 50%. FVC <50% occurred in 5 cases (38.4%), FVC% 50-69% in 6 cases (46.1%) and FVC>70% in other two cases. Considering individualized score of severity, case 7 had the highest score (24), a neonatal form and the only wheelchair bound of the cohort. Another 23% had a score equal to or above 20. CNM intermediate severity, scores 11 to 15, was observed in 53.8% of the cohort and 15.3% had minor scores of 6 and 9. This was associated with CNM with onset in adults, patients with long disease duration. In conclusion: the instruments MFM 32-P and MIF allowed to characterize the phenotypic spectrum of MCN and showed variability within families members. It was found positive and significant correlation between phenotypic severity detected by MFM 32-P and MIF in their total scores and between the D1-MFM 32-P and the sub domains mobility, locomotion and self-care of FIM scale. There was no correlation between lung function, MFM 32-P or FIM / Mestrado / Ciencias Biomedicas / Mestra em Ciências Médicas