A Miopatia Centronuclear (MCN) é uma doença neuromuscular hereditária (genética). Ela se manifesta com sintomas de fraqueza muscular presentes desde o nascimento (uma condição chamada miopatia congênita) e por uma característica vista na biópsia muscular: os núcleos das células musculares ficam localizados no centro.
Introdução
O que você precisa saber de cara
A Miopatia Centronuclear (MCN) é uma doença neuromuscular hereditária (genética). Ela se manifesta com sintomas de fraqueza muscular presentes desde o nascimento (uma condição chamada miopatia congênita) e por uma característica vista na biópsia muscular: os núcleos das células musculares ficam localizados no centro.
Escala de raridade
<1/50kMuito rara
1/20kRara
1/10kPouco freq.
1/5kIncomum
1/2k
Encontrou um erro ou informação desatualizada? Sugira uma correção →
Entender a doença
Do básico ao detalhe, leia no seu ritmo
Preparando trilha educativa...
Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 61 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 154 características clínicas mais associadas, ordenadas por frequência.
Linha do tempo da pesquisa
Encontrou um erro ou informação desatualizada? Sugira uma correção →
Genética e causas
O que está alterado no DNA e como passa nas famílias
Genes associados
11 genes identificados com associação a esta condição. Padrão de herança: Autosomal dominant, Autosomal recessive, X-linked recessive.
Component of the deuterosome, a structure that promotes de novo centriole amplification in multiciliated cells that can generate more than 100 centrioles. Deuterosome-mediated centriole amplification occurs in terminally differentiated multiciliated cells (G1/0) and not in S phase. Essential for centriole amplification and is required for CEP152 localization to the deuterosome
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centrioleCytoplasm, perinuclear regionCell membrane, sarcolemmaSarcoplasmic reticulum
Myopathy, centronuclear, 4
A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers.
Lipid phosphatase that specifically dephosphorylates the D-3 position of phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, generating phosphatidylinositol and phosphatidylinositol 5-phosphate
Cytoplasm
Myopathy, centronuclear, 1
A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers.
Involved in muscle differentiation (myogenic factor). Induces fibroblasts to differentiate into myoblasts. Probable sequence specific DNA-binding protein
Nucleus
Transactivates the HES3 promoter independently of NOTCH proteins. HES3 is a non-canonical NOTCH target gene which lacks binding sites for RBPJ
Nucleus
Hypospadias 2, X-linked
A common malformation in which the urethra opens on the ventral side of the penis, due to developmental arrest of urethral fusion. The opening can be located glandular, penile, or even more posterior in the scrotum or perineum. Hypospadias is a feature of several syndromic disorders, including the androgen insensitivity syndrome and Opitz syndrome.
Key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The size and extensibility of the cross-links are the main determinants of sarcomere extensibility properties of muscle. In non-muscle cells, seems to play a role in chromosome condensation and chromosome segregation during mitosis. Might link the lamina network to ch
CytoplasmNucleus
Myopathy, myofibrillar, 9, with early respiratory failure
An autosomal dominant myopathy characterized by adulthood onset of weakness in proximal, distal, axial and respiratory muscles. Pelvic girdle weakness, foot drop and neck weakness are the main symptoms at onset, but ultimately the weakness usually involves the proximal compartment of both upper and lower limbs. Additional features include variable degrees of Achilles tendon contractures, spinal rigidity and muscle hypertrophy. Respiratory involvement often leads to requirement for non-invasive ventilation support.
Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules (PubMed:11741831, PubMed:16163667, PubMed:18268335, PubMed:18650434, PubMed:26115329). Repeated very high-level exercise increases the open probability of the channel and leads to Ca(2+) leaking into the cytoplasm (PubMed:18268335). Can also mediate the release of Ca(2+)
Sarcoplasmic reticulum membrane
Malignant hyperthermia 1
Autosomal dominant pharmacogenetic disorder of skeletal muscle and is one of the main causes of death due to anesthesia. In susceptible people, an MH episode can be triggered by all commonly used inhalational anesthetics such as halothane and by depolarizing muscle relaxants such as succinylcholine. The clinical features of the myopathy are hyperthermia, accelerated muscle metabolism, contractures, metabolic acidosis, tachycardia and death, if not treated with the postsynaptic muscle relaxant, dantrolene. Susceptibility to MH can be determined with the 'in vitro' contracture test (IVCT): observing the magnitude of contractures induced in strips of muscle tissue by caffeine alone and halothane alone. Patients with normal response are MH normal (MHN), those with abnormal response to caffeine alone or halothane alone are MH equivocal (MHE(C) and MHE(H) respectively).
Is a key player in the control of plasma membrane curvature, membrane shaping and membrane remodeling. Required in muscle cells for the formation of T-tubules, tubular invaginations of the plasma membrane that function in depolarization-contraction coupling (PubMed:24755653). Is a negative regulator of endocytosis (By similarity). Is also involved in the regulation of intracellular vesicles sorting, modulation of BACE1 trafficking and the control of amyloid-beta production (PubMed:27179792). In
NucleusCytoplasmEndosomeCell membrane, sarcolemma, T-tubule
Myopathy, centronuclear, 2
A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers.
Catalyzes the hydrolysis of GTP and utilizes this energy to mediate vesicle scission at plasma membrane during endocytosis and filament remodeling at many actin structures during organization of the actin cytoskeleton (PubMed:15731758, PubMed:19605363, PubMed:19623537, PubMed:33713620, PubMed:34744632). Plays an important role in vesicular trafficking processes, namely clathrin-mediated endocytosis (CME), exocytic and clathrin-coated vesicle from the trans-Golgi network, and PDGF stimulated macr
Cytoplasm, cytoskeletonCytoplasmic vesicle, clathrin-coated vesicleCell projection, uropodiumEndosomeCytoplasm, cytoskeleton, microtubule organizing center, centrosomeCytoplasm, cytoskeleton, microtubule organizing center, centrosome, centrioleRecycling endosomeCell projection, phagocytic cupCytoplasmic vesicle, phagosome membraneCell projection, podosomeCytoplasmCell junctionPostsynaptic densitySynapse, synaptosomeMidbodyMembrane, clathrin-coated pit
Myopathy, centronuclear, 1
A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers.
Stress-activated component of a protein kinase signal transduction cascade that promotes programmed cell death in response to various stress, such as ribosomal stress, osmotic shock and ionizing radiation (PubMed:10924358, PubMed:11836244, PubMed:12220515, PubMed:14521931, PubMed:15350844, PubMed:15737997, PubMed:18331592, PubMed:20559024, PubMed:26999302, PubMed:32289254, PubMed:32610081, PubMed:35857590). Acts by catalyzing phosphorylation of MAP kinase kinases, leading to activation of the JN
CytoplasmNucleus
Split-foot malformation with mesoaxial polydactyly
An autosomal recessive disorder characterized by a split-foot defect, mesoaxial polydactyly, nail abnormalities of the hands, and sensorineural hearing loss.
Isoform 3 may have a role in regulating the growth and differentiation of arterial smooth muscle cells
Nucleus
Myopathy, centronuclear, 5
A form of centronuclear myopathy, a congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers. CNM5 features include severe neonatal hypotonia with respiratory insufficiency, difficulty feeding, and delayed motor development. Some patients die in infancy, and some develop dilated cardiomyopathy.
Lipid phosphatase which dephosphorylates phosphatidylinositol 3-monophosphate (PI3P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) (PubMed:10900271, PubMed:11001925, PubMed:12646134, PubMed:14722070). Has also been shown to dephosphorylate phosphotyrosine- and phosphoserine-containing peptides (PubMed:9537414). Negatively regulates EGFR degradation through regulation of EGFR trafficking from the late endosome to the lysosome (PubMed:14722070). Plays a role in vacuolar formation and morph
CytoplasmCell membraneCell projection, filopodiumCell projection, ruffleLate endosomeCytoplasm, myofibril, sarcomere
Myopathy, centronuclear, X-linked
A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers.
Variantes genéticas (ClinVar)
147 variantes patogênicas registradas no ClinVar.
Classificação de variantes (ClinVar)
Distribuição de 290 variantes classificadas pelo ClinVar.
Vias biológicas (Reactome)
33 vias biológicas associadas aos genes desta condição.
Diagnóstico
Os sinais que médicos procuram e os exames que confirmam
Tratamento e manejo
Remédios, cuidados de apoio e o que precisa acompanhar
Onde tratar no SUS
Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)
🇧🇷 Atendimento SUS — Miopatia centronuclear
Selecione um estado ou use sua localização para ver resultados.
Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.
Pesquisa ativa
Ensaios clínicos abertos e novidades científicas recentes
Ensaios em destaque
🟢 Recrutando agora
6 pesquisas recrutando participantes. Converse com seu médico sobre a possibilidade de participar.
Outros ensaios clínicos
22 ensaios clínicos encontrados, 7 ativos.
Publicações mais relevantes
Muscle-Specific DNM2 Overexpression Improves Charcot-Marie-Tooth Disease In Vivo and Reveals a Narrow Therapeutic Window in Skeletal Muscle.
Charcot-Marie-Tooth disease (CMT), caused by dominant loss-of-function mutations in DNM2, encoding the GTPase dynamin-2, impairs motor and sensory function. However, the respective contributions of muscle and nerve pathology, and the therapeutic potential of increasing DNM2 expression, remain unresolved. We evaluated tissue-targeted and systemic approaches to increase DNM2 in a mouse model carrying the common K562E-CMT mutation. Muscle-specific DNM2 overexpression from embryogenesis in Dnm2K562E/+ mice ameliorated desmin and integrin mislocalization, membrane trafficking defects, mitochondrial abnormalities, and fibrosis in skeletal muscle, resulting in improved locomotor coordination despite persistent muscle atrophy. Conversely, systemic postnatal AAV delivery of human DNM2 increased DNM2 in muscle but failed to transduce nerves and paradoxically worsened the muscle pathology, producing centronuclear myopathy-like features. These findings reveal a primary pathogenic impact of DNM2-CMT mutation within skeletal muscle, independent of nerve involvement. Collectively, they underscore that precise DNM2 dosage is critical for neuromuscular homeostasis and reveal a narrow therapeutic window for safe and effective therapeutic intervention. This paradox, in which efforts to compensate for a loss-of-function neuropathy risk inducing a gain-of-function myopathy, highlights the need for tightly controlled modulation of DNM2 activity in future therapeutic strategies.
Incidence and Prevalence of Congenital Myopathies - A Population-Based Study From Western Sweden.
Congenital myopathies are a group of rare genetic muscle disorders. Previous studies have estimated point prevalences which only include surviving individuals. Our aim was to perform an epidemiological study with strict inclusion criteria, using modern diagnostic technology to present both incidences and prevalences, and to describe the genetic and muscle pathological characteristics of these disorders. A retrospective, population-based epidemiological study was conducted in western Sweden between 1985 and 2022. All patients diagnosed with congenital myopathies during this period were included. In total, 104 patients were identified whereas 25 died during the follow-up. The total birth prevalence (estimated lifetime risk) was 14.9 per 100,000 live births, whereas the total cumulative incidence by age 35 years was 12.3 per 100,000 inhabitants, and the total point prevalence was 3.9 per 100,000 inhabitants. The most common histopathological type was congenital myopathy with nonspecific changes (birth prevalence 4.1 per 100,000 live births), followed by core myopathy and centronuclear myopathy (2.1 per 100,000). The most common causative genes were MYH2 (3.9 per 100,000) and RYR1 (2.0 per 100,000). Despite using next-generation sequencing, 1 in 5 cases lacked a genetic diagnosis. Among those without a genetic cause, 4 of 5 had nonspecific histopathological changes. By including all patients identified, both alive and deceased, our estimated incidence figures are considerably higher than estimates of point prevalence, which only includes living patients. As the mortality in these diseases is significant, incidence figures better reflect the occurrence in the population and are important for evidence-based health care planning and resource allocation. ANN NEUROL 2026;99:382-392.
Liver health in myotubular and centronuclear myopathies: a patient-driven data collection study to better understand liver health and improve standards of care.
Liver health issues in X-linked myotubular myopathy and centronuclear myopathies have historically been under-recognized, with liver monitoring not a routine focus of clinical care. Anecdotal case reports and liver-related adverse events in recent clinical trials highlight the growing need to better understand liver involvement in this population. A patient-led initiative brought together a multi-stakeholder expert working group, the 'Myotubular and Centronuclear Myopathy Global Liver Collaborative' who developed a liver health questionnaire to collect longitudinal patient-reported liver health data. Data from 219 participants was analysed and liver abnormalities were found to be most prevalent in myotubular myopathy patients with 36 % of affected males having abnormal liver function tests with liver issues also reported by symptomatic female carriers. Patients with liver abnormalities were also more likely to require invasive ventilation and had poorer motor function, suggesting a link between liver health and overall disease severity. Significant variation in liver monitoring was observed, with 30 % of participants never having undergone liver function blood tests demonstrating the need for routine liver screening to inform standards of care and guide clinical management. The patient-driven Liver Collaborative has been instrumental in raising awareness in liver related issues with clinical and patient communities.
Integrative Multi-Omics and Network Analyses Reveal Pathogenic and Protective Pathways in Centronuclear Myopathies.
Centronuclear and myotubular myopathies (CNMs) are rare, inherited muscle disorders characterized by muscle atrophy, weakness, and altered muscle fiber structure, primarily caused by mutations in MTM1, DNM2, or BIN1. The molecular mechanisms driving CNM are only partially understood, and no curative therapies are available. To elucidate molecular pathways involved in CNMs, we present an integrative multi-omics analysis across several CNM mouse models untreated or treated with pre-clinical strategies, combining transcriptomic, proteomic, and metabolomic datasets with curated interaction, metabolic, tissue, and phenotype knowledge using network-based approaches. Weighted Gene Co-expression Network Analysis (WGCNA) identified gene modules commonly altered in three CNM genetic forms. Modules correlated with improved muscle function were enriched for processes such as muscle contraction, RNA metabolism, and oxidative phosphorylation, whereas modules linked to disease severity were enriched for immune response, innervation, vascularization, and fatty acid oxidation. We further integrated transcriptomic, proteomic, and metabolomic data from the Mtm1-/y mouse model with public knowledge bases into a multilayer network, and explored it using a random walk with restart approach. These analyses highlighted metabolites closely connected to CNM phenotypes, some of which may represent candidates for nutritional or pharmacological modulation. Our findings illustrate how integrative multi-omics and network analyses reveal both pathogenic and protective pathways in CNM and provide a foundation for identifying novel therapeutic opportunities.
Ca2+, ROS, IL-6, and p38 MAPK signaling loops underlying alterations in myotube formation induced by a severe MH/CCD mutation in RyR1.
Mutations in the gene encoding the skeletal muscle ryanodine receptor (RyR1) can result in muscle diseases, termed RyR1-related myopathies (RyR1-RM). Examples include malignant hyperthermia (MH), central core disease (CCD), and centronuclear myopathy (CNM). The muscles involved often have more (and mispositioned) nuclei than normal. A subset of the corresponding mutant proteins shows an overactive or leaky sarcoplasmic reticulum (SR) channel behavior that depletes the SR Ca2+ content and increases the level of cytosolic Ca2+. In addition, two remarkable effects of these RyR1 variants have been reported in cultured myogenic cells: enhanced expression of interleukin-6 (IL-6) and stimulation of myoblast fusion (myonuclei accretion). Here, we have investigated whether the latter effect is due to a possible IL-6-dependent autocrine loop. Toward this goal, we analyzed the impact of the overactive Y523S mutant compared with the wild-type RyR1 after expression in C2C12 cells. The results show that this mutation indeed drastically promotes myoblast fusion up to ∼300%. Moreover, this action depends on the sequential activation of SR Ca2+ release, store-operated Ca2+ channels, reactive oxygen species (ROS, cytosolic and mitochondrial), calpain, and calcineurin. In addition, a neutralizing antibody directed against IL-6 and a p38 inhibitor completely suppressed the stimulation of myoblast fusion. Furthermore, in RyR1-expressing cells, myotube formation was promoted by either exogenous IL-6 or conditioned medium obtained from the Y523S-expressing cells. These findings suggest an autocrine mechanism involving the interplay between Ca2+, ROS, IL-6, and p38 signaling pathways in controlling myonuclei density, which could be essential to explain the pathogenesis of RyR1-RM.NEW & NOTEWORTHY Overactive RyR1 mutant proteins are associated with muscle disease; interestingly, they increase the number of myonuclei when expressed in C2C12 cells. We discovered that this alteration depends on a Ca2+/ROS loop, which recruits calpain and calcineurin to stimulate the production of IL-6 and the subsequent autocrine activation of p38. Thus, disease-causing RyR1 mutations require an IL-6 autocrine system to alter myonuclear density. This novel mechanism could be critical to understanding the pathogenesis of congenital myopathies.
Publicações recentes
X-linked myotubular myopathy in a neonate: a case report and literature review.
Polymorphic myopathological findings in a 77-year-old woman with oculo-bulbo-facial and distal weakness.
Liver health in myotubular and centronuclear myopathies: a patient-driven data collection study to better understand liver health and improve standards of care.
Muscle-Specific DNM2 Overexpression Improves Charcot-Marie-Tooth Disease In Vivo and Reveals a Narrow Therapeutic Window in Skeletal Muscle.
🥇 Ensaio randomizadoTamoxifen treatment fails to improve muscle dysfunction in a model of recessive RYR1-linked centronuclear myopathy.
📚 EuropePMC272 artigos no totalmostrando 200
Liver health in myotubular and centronuclear myopathies: a patient-driven data collection study to better understand liver health and improve standards of care.
Neuromuscular disorders : NMDMuscle-Specific DNM2 Overexpression Improves Charcot-Marie-Tooth Disease In Vivo and Reveals a Narrow Therapeutic Window in Skeletal Muscle.
International journal of molecular sciencesTamoxifen treatment fails to improve muscle dysfunction in a model of recessive RYR1-linked centronuclear myopathy.
Disease models & mechanismsIntegrative Multi-Omics and Network Analyses Reveal Pathogenic and Protective Pathways in Centronuclear Myopathies.
International journal of molecular sciencesCa2+, ROS, IL-6, and p38 MAPK signaling loops underlying alterations in myotube formation induced by a severe MH/CCD mutation in RyR1.
American journal of physiology. Cell physiologyIncidence and Prevalence of Congenital Myopathies - A Population-Based Study From Western Sweden.
Annals of neurologyClinical and Genetic Spectrum of Titinopathy: A Turkish Pediatric Case Series.
Neuro endocrinology letters[Clinical and genetic features of 5 neonates with centronuclear myopathy caused by MTM1 gene variation].
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatricsGene replacement therapy for centronuclear myopathy: A breakthrough in complex genetic muscle disease.
Molecular therapy : the journal of the American Society of Gene TherapyNOTCH2 mutation in centronuclear myopathy: Beyond the scope.
Molecular therapy : the journal of the American Society of Gene TherapyIdentification of a novel MTM1 pathogenic variant in neonatal X-linked centronuclear myopathy: a case report from East Asia.
Acta neurologica BelgicaExon skipping peptide-conjugated morpholinos downregulate dynamin 2 to rescue centronuclear myopathy.
Brain : a journal of neurologyA systematic review on motor outcome measures in congenital myopathy.
Neuromuscular disorders : NMDCombining dynamin 2 myopathy and neuropathy mutations rescues both phenotypes.
Nature communicationsUnderstanding the role of NOTCH2 mutation in centronuclear myopathy.
Molecular therapy : the journal of the American Society of Gene TherapyBIN1 gene replacement reverses BIN1-related centronuclear myopathy.
Molecular therapy : the journal of the American Society of Gene TherapyLiver function in X-linked myotubular myopathy and autosomal dominant centronuclear myopathy: Data of the unite-CNM study.
Journal of neuromuscular diseasesEvaluation of dynamin 2 knockdown as a therapeutic strategy for RYR1 related myopathy.
Neuromuscular disorders : NMDA novel DNM2 variant associated with centronuclear myopathy: a case report.
Frontiers in geneticsThe synaptic availability of GluA1 is reduced in hippocampal neurons of a murine model of dynamin-2 linked autosomal dominant centronuclear myopathy.
Science progressSH3KBP1 promotes skeletal myofiber formation and functionality through ER/SR architecture integrity.
EMBO reportsBIN1 reduction ameliorates DNM2-related Charcot-Marie-Tooth neuropathy.
Proceedings of the National Academy of Sciences of the United States of AmericaX-linked myotubular myopathy: an untreated treatable disease.
Expert opinion on biological therapyA novel transgenic reporter of extracellular acidification in zebrafish elucidates skeletal muscle T-tubule pH regulation.
Developmental dynamics : an official publication of the American Association of AnatomistsEuropean EHBP1L1 Genotyping Survey of Dyserythropoietic Anemia and Myopathy Syndrome in English Springer Spaniels.
Veterinary sciencesA Novel Mutation Associated with Severe Centronuclear Myopathy in a Neonate.
Neurology IndiaPotential compensatory mechanisms preserving cardiac function in myotubular myopathy.
Cellular and molecular life sciences : CMLSEffect of Pathogenic Mutations on the Formation of High-Order Dynamin 2 Assemblies in Living Cells.
BiochemistryCCDC78: Unveiling the Function of a Novel Gene Associated with Hereditary Myopathy.
CellsDynamin-2 mutations linked to neonatal-onset centronuclear myopathy impair exocytosis and endocytosis in adrenal chromaffin cells.
Journal of neurochemistryUncovering the BIN1-SH3 interactome underpinning centronuclear myopathy.
eLifeExome sequencing in undiagnosed congenital myopathy reveals new genes and refines genes-phenotypes correlations.
Genome medicinePhenotype-Genotype Correlation of a Cohort of Patients with Congenital Myopathy: A Single Centre Experience from India.
Journal of neuromuscular diseases[Clinical characteristics and genetic analysis of two children with X-linked Centronuclear myopathy due to variants of MTM1 gene].
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical geneticsThe Influence of a Genetic Variant in CCDC78 on LMNA-Associated Skeletal Muscle Disease.
International journal of molecular sciencesIntegrated multi-omics approach reveals the role of striated muscle preferentially expressed protein kinase in skeletal muscle including its relationship with myospryn complex.
Journal of cachexia, sarcopenia and muscleLessons Learned From Clinical Studies in Centronuclear Myopathies: The Patient Perspective-A Qualitative Study.
Clinical therapeuticsAmphiphysin-2 (BIN1) functions and defects in cardiac and skeletal muscle.
Trends in molecular medicineThe experience of clinical study and trial participation in rare diseases: A scoping review of centronuclear myopathy and other neuromuscular disorders.
Neuromuscular disorders : NMDPrognostic Value of Genotype-Phenotype Correlations in X-Linked Myotubular Myopathy and the Use of the Face2Gene Application as an Effective Non-Invasive Diagnostic Tool.
GenesEffects of gene replacement therapy with resamirigene bilparvovec (AT132) on skeletal muscle pathology in X-linked myotubular myopathy: results from a substudy of the ASPIRO open-label clinical trial.
EBioMedicineThe myotubular and centronuclear myopathy patient registry: a multifunctional tool for translational research.
Neuromuscular disorders : NMDA brief history of the congenital myopathies - the myopathological perspective.
Neuromuscular disorders : NMD[The dynamin-2-gene related centronuclear myopathy].
Medecine sciences : M/SSuccessful treatment of frequent premature ventricular contractions and non-sustained ventricular tachycardia with verapamil and flecainide in RYR1-related myopathy: a case report.
European heart journal. Case reportsShaping transverse-tubules: central mechanisms that play a role in the cytosol zoning for muscle contraction.
Journal of biochemistrySpeg interactions that regulate the stability of excitation-contraction coupling protein complexes in triads and dyads.
Communications biologyNovel SPEG variants in a neonate with severe dilated cardiomyopathy and relatively mild hypotonia.
Human genome variationDNM2 levels normalization improves muscle phenotypes of a novel mouse model for moderate centronuclear myopathy.
Molecular therapy. Nucleic acidsMTM1 overexpression prevents and reverts BIN1-related centronuclear myopathy.
Brain : a journal of neurology"Gearing" up for dynamin-catalyzed membrane fission.
Current opinion in cell biologyA Possible Case of Centronuclear Myopathy: A Case Report.
Medicina (Kaunas, Lithuania)Respiratory features of centronuclear myopathy in the Netherlands.
Neuromuscular disorders : NMDA centronuclear myopathy-causing mutation in dynamin-2 disrupts neuronal morphology and excitatory synaptic transmission in a murine model of the disease.
Neuropathology and applied neurobiologyExtremely thinning ribs in severe congenital myopathy.
Pediatric pulmonologyDynamins in human diseases: differential requirement of dynamin activity in distinct tissues.
Current opinion in cell biologyX-Linked Myotubular Myopathy in a Female Patient with a Pathogenic Variant in the MTM1 Gene.
International journal of molecular sciencesIntegrated multi-omics approach reveals the role of SPEG in skeletal muscle biology including its relationship with myospryn complex.
bioRxiv : the preprint server for biologyEHBP1L1, an apicobasal polarity regulator, is critical for nuclear polarization during enucleation of erythroblasts.
Blood advancesX-linked myotubular myopathy: a clinical report and a review of the mild phenotype.
Revista de neurologiaInactivating the lipid kinase activity of PI3KC2β is sufficient to rescue myotubular myopathy in mice.
JCI insightTamoxifen improves muscle structure and function of Bin1- and Dnm2-related centronuclear myopathies.
Brain : a journal of neurologyEndosomal lipid signaling reshapes the endoplasmic reticulum to control mitochondrial function.
Science (New York, N.Y.)Therapeutic approaches in different congenital myopathies.
Current opinion in pharmacologyNot young but still immature: a HIF-1α-mediated maturation checkpoint in regenerating muscle.
The Journal of clinical investigationDifferential impact of ubiquitous and muscle dynamin 2 isoforms in muscle physiology and centronuclear myopathy.
Nature communicationsPhenotypic Spectrum of DNM2-Related Centronuclear Myopathy.
Neurology. GeneticsA novel MAP3K20 mutation causing centronuclear myopathy-6 with fiber-type disproportion in a Pakistani family.
Journal of human geneticsAntagonistic control of active surface integrins by myotubularin and phosphatidylinositol 3-kinase C2β in a myotubular myopathy model.
Proceedings of the National Academy of Sciences of the United States of AmericaGain-of-Function Dynamin-2 Mutations Linked to Centronuclear Myopathy Impair Ca2+-Induced Exocytosis in Human Myoblasts.
International journal of molecular sciencesNovel Splicing Mutation in MTM1 Leading to Two Abnormal Transcripts Causes Severe Myotubular Myopathy.
International journal of molecular sciencesEHBP1L1 Frameshift Deletion in English Springer Spaniel Dogs with Dyserythropoietic Anemia and Myopathy Syndrome (DAMS) or Neonatal Losses.
GenesA mitofusin 2/HIF1α axis sets a maturation checkpoint in regenerating skeletal muscle.
The Journal of clinical investigationDevelopment of versatile allele-specific siRNAs able to silence all the dominant dynamin 2 mutations.
Molecular therapy. Nucleic acidsA case of giant dental calculus in a patient with centronuclear myopathy.
Special care in dentistry : official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric DentistryAn EHPB1L1 Nonsense Mutation Associated with Congenital Dyserythropoietic Anemia and Polymyopathy in Labrador Retriever Littermates.
GenesDynamin-2 reduction rescues the skeletal myopathy of a SPEG-deficient mouse model.
JCI insightINCEPTUS Natural History, Run-in Study for Gene Replacement Clinical Trial in X-Linked Myotubular Myopathy.
Journal of neuromuscular diseasesCentronuclear Myopathy Caused by Defective Membrane Remodelling of Dynamin 2 and BIN1 Variants.
International journal of molecular sciencesA review of major causative genes in congenital myopathies.
Journal of human geneticsNatural history study and statistical modeling of disease progression in a preclinical model of myotubular myopathy.
Disease models & mechanismsDilated-Left Ventricular Non-Compaction Cardiomyopathy in a Pediatric Case with SPEG Compound Heterozygous Variants.
International journal of molecular sciencesCongenital myopathies: The current status.
Indian journal of pathology & microbiologyCharacterization of a novel zebrafish model of SPEG-related centronuclear myopathy.
Disease models & mechanismsBenefits of therapy by dynamin-2-mutant-specific silencing are maintained with time in a mouse model of dominant centronuclear myopathy.
Molecular therapy. Nucleic acidsA dog model for centronuclear myopathy carrying the most common DNM2 mutation.
Disease models & mechanismsCorrigendum: A Systematic Review and Meta-Analysis of the Prevalence of Congenital Myopathy.
Frontiers in neurologyBIN1 modulation in vivo rescues dynamin-related myopathy.
Proceedings of the National Academy of Sciences of the United States of AmericaHereditary myopathies associated with hematological abnormalities.
Muscle & nerveImaging-based evaluation of pathogenicity by novel DNM2 variants associated with centronuclear myopathy.
Human mutationA Systematic Review and Meta-Analysis of the Prevalence of Congenital Myopathy.
Frontiers in neurologyCommon Pathogenic Mechanisms in Centronuclear and Myotubular Myopathies and Latest Treatment Advances.
International journal of molecular sciencesGain-of-Function Properties of a Dynamin 2 Mutant Implicated in Charcot-Marie-Tooth Disease.
Frontiers in cellular neuroscienceA Novel SPEG mutation causing congenital myopathy with fiber size disproportion and dilated cardiomyopathy with heart transplantation.
Neuromuscular disorders : NMDMutational and clinical spectrum of centronuclear myopathy in 9 cases and a literature review of Chinese patients.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical NeurophysiologyA recurrent RYR1 mutation associated with early-onset hypotonia and benign disease course.
Acta neuropathologica communicationsMild congenital myopathy due to a novel variation in SPEG gene.
Intractable & rare diseases researchClinical, genetic, and histological features of centronuclear myopathy in the Netherlands.
Clinical geneticsMice with muscle-specific deletion of Bin1 recapitulate centronuclear myopathy and acute downregulation of dynamin 2 improves their phenotypes.
Molecular therapy : the journal of the American Society of Gene TherapyCentronuclear myopathy due to a de novo nonsense variant and a maternally inherited splice-site variant in TTN: A case report.
Clinical case reportsMarked Facial Weakness, Ptosis, and Hanging Jaw: A Case with RYR1 -Related Congenital Centronuclear Myopathy.
Journal of pediatric geneticsCongenital Myopathies: A Clinicopathological Study of 10 Cases in a Tertiary Care Hospital of North India.
Journal of pediatric neurosciencesFunctional Characterization of Endogenously Expressed Human RYR1 Variants.
Journal of visualized experiments : JoVEThe spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorders due to defective autophagy.
AutophagyStriated Preferentially Expressed Protein Kinase (SPEG) in Muscle Development, Function, and Disease.
International journal of molecular sciencesX-Linked Myotubular Myopathy: A Novel Mutation Expanding the Genotypic Spectrum of a Phenotypically Heterogeneous Myopathy.
Journal of pediatric geneticsMulti-omics comparisons of different forms of centronuclear myopathies and the effects of several therapeutic strategies.
Molecular therapy : the journal of the American Society of Gene TherapyClinical and genetic analysis of a case with centronuclear myopathy caused by SPEG gene mutation: a case report and literature review.
BMC pediatricsSatellite cells deficiency and defective regeneration in dynamin 2-related centronuclear myopathy.
FASEB journal : official publication of the Federation of American Societies for Experimental BiologyRefractory rhabdomyolysis responsive to corticosteroid therapy.
Proceedings (Baylor University. Medical Center)Symptomatic heterozygous X-Linked myotubular myopathy female patient with a large deletion at Xq28 and decrease expression of normal allele.
European journal of medical geneticsA new mutation in DNM2 gene in a large Italian family.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical NeurophysiologyHierarchical Bayesian modelling of disease progression to inform clinical trial design in centronuclear myopathy.
Orphanet journal of rare diseasesSPEG binds with desmin and its deficiency causes defects in triad and focal adhesion proteins.
Human molecular geneticsMutant BIN1-Dynamin 2 complexes dysregulate membrane remodeling in the pathogenesis of centronuclear myopathy.
The Journal of biological chemistryDiagnosing X-linked Myotubular Myopathy - A German 20-year Follow Up Experience.
Journal of neuromuscular diseasesThe translational value of animal models in orphan medicines designations for rare paediatric neurological diseases.
Regulatory toxicology and pharmacology : RTPDynamin-2 Regulates Postsynaptic Cytoskeleton Organization and Neuromuscular Junction Development.
Cell reportsDynamin-2 R465W mutation induces long range perturbation in highly ordered oligomeric structures.
Scientific reportsSPEG: a key regulator of cardiac calcium homeostasis.
Cardiovascular researchDifferential physiological roles for BIN1 isoforms in skeletal muscle development, function and regeneration.
Disease models & mechanismsA case of de novo dynamin 2 (DNM2)-related centronuclear myopathy with electrical but not clinical myotonia.
Chinese medical journalPhysiological impact and disease reversion for the severe form of centronuclear myopathy linked to dynamin.
JCI insightRegulation of myonuclear positioning and muscle function by the skeletal muscle-specific CIP protein.
Proceedings of the National Academy of Sciences of the United States of AmericaScission, a critical step in autophagosome formation.
AutophagyMyostatin: a Circulating Biomarker Correlating with Disease in Myotubular Myopathy Mice and Patients.
Molecular therapy. Methods & clinical developmentBi-allelic expression of the RyR1 p.A4329D mutation decreases muscle strength in slow-twitch muscles in mice.
The Journal of biological chemistryA location, location, location mutation impairs DNM2-mediated release of nascent autophagosomes from recycling endosomes.
AutophagyA mutation in MTM1 causes X-Linked myotubular myopathy in Boykin spaniels.
Neuromuscular disorders : NMDThe intragenic microRNA miR199A1 in the dynamin 2 gene contributes to the pathology of X-linked centronuclear myopathy.
The Journal of biological chemistryA DNM2 Centronuclear Myopathy Mutation Reveals a Link between Recycling Endosome Scission and Autophagy.
Developmental cellTargeted Treatments for Inherited Neuromuscular Diseases of Childhood.
Seminars in neurologyCentronuclear Myopathy with Abundant Nemaline Rods in a Japanese Black and Hereford Crossbred Calf.
Journal of comparative pathologyProtein Amphipathic Helix Insertion: A Mechanism to Induce Membrane Fission.
Frontiers in cell and developmental biologyInsights into wild-type dynamin 2 and the consequences of DNM2 mutations from transgenic zebrafish.
Human molecular geneticsGenotype-Phenotype Correlations in Charcot-Marie-Tooth Disease Due to MTMR2 Mutations and Implications in Membrane Trafficking.
Frontiers in neuroscienceParaspinal amyotrophy in DNM-2-related centronuclear myopathy.
Journal of the neurological sciencesDifferent in vivo impacts of dynamin 2 mutations implicated in Charcot-Marie-Tooth neuropathy or centronuclear myopathy.
Human molecular geneticsNovel SPEG variant cause centronuclear myopathy in China.
Journal of clinical laboratory analysisAutophagy Defects in Skeletal Myopathies.
Annual review of pathologyMortality and respiratory support in X-linked myotubular myopathy: a RECENSUS retrospective analysis.
Archives of disease in childhoodThe Dog Model in the Spotlight: Legacy of a Trustful Cooperation.
Journal of neuromuscular diseasesA homozygous mutation in GMPPB leads to centronuclear myopathy with combined pre- and postsynaptic defects of neuromuscular transmission.
Neuromuscular disorders : NMDTherapeutic Aspects in Congenital Myopathies.
Seminars in pediatric neurologyQuantitative RyR1 reduction and loss of calcium sensitivity of RyR1Q1970fsX16+A4329D cause cores and loss of muscle strength.
Human molecular geneticsEDTP/MTMR14: A novel target for improved survivorship to prolonged anoxia and cellular protein aggregates.
Neuroscience lettersCorrelative SICM-FCM reveals changes in morphology and kinetics of endocytic pits induced by disease-associated mutations in dynamin.
FASEB journal : official publication of the Federation of American Societies for Experimental BiologyAllele-Specific CRISPR/Cas9 Correction of a Heterozygous DNM2 Mutation Rescues Centronuclear Myopathy Cell Phenotypes.
Molecular therapy. Nucleic acidsNuclear defects in skeletal muscle from a Dynamin 2-linked centronuclear myopathy mouse model.
Scientific reportsCentronuclear myopathy with cardiomyopathy due to recessive titinopathy.
Muscle & nerve'Dusty core disease' (DuCD): expanding morphological spectrum of RYR1 recessive myopathies.
Acta neuropathologica communicationsClathrin plaques and associated actin anchor intermediate filaments in skeletal muscle.
Molecular biology of the cellNeuromuscular transmission defects in myopathies: Rare but worth searching for.
Muscle & nerveDownregulation of EDTP in glial cells suppresses polyglutamine protein aggregates and extends lifespan in Drosophila melanogaster.
Neuroscience lettersDynamin 2 (DNM2) as Cause of, and Modifier for, Human Neuromuscular Disease.
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeuticsRyanodine Receptor 1-Related Myopathies: Diagnostic and Therapeutic Approaches.
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeuticsReducing dynamin 2 (DNM2) rescues DNM2-related dominant centronuclear myopathy.
Proceedings of the National Academy of Sciences of the United States of AmericaNon-compaction cardiomyopathy and early respiratory failure in an adult symptomatic female carrier of centronuclear myopathy caused by a MTM1 mutation.
Neuromuscular disorders : NMDSome DNM2 mutations cause extremely severe congenital myopathy and phenocopy myotubular myopathy.
Acta neuropathologica communicationsA novel SPEG mutation causes non-compaction cardiomyopathy and neuropathy in a floppy infant with centronuclear myopathy.
Acta neuropathologica communicationsNew variant of necklace fibres display peculiar lysosomal structures and mitophagy.
Neuromuscular disorders : NMDAn integrated modelling methodology for estimating the prevalence of centronuclear myopathy.
Neuromuscular disorders : NMDCentronuclear myopathies under attack: A plethora of therapeutic targets.
Journal of neuromuscular diseases[Centronuclear myopathy: clinical characteristics and MRI image features of oral and maxillofacial region].
Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatologyA Roma founder BIN1 mutation causes a novel phenotype of centronuclear myopathy with rigid spine.
NeurologyDifferential Expression of Several miRNAs and the Host Genes AATK and DNM2 in Leukocytes of Sporadic ALS Patients.
Frontiers in molecular neuroscienceCharacterization of congenital myopathies at a Korean neuromuscular center.
Muscle & nerveGiant biventricular aneurysms: a novel cardiac phenotype in myotubular/centronuclear myopathy.
European heart journalLabel-free identification of myopathological features with coherent anti-Stokes Raman scattering.
Muscle & nerveNovel SPEG Mutations in Congenital Myopathy without Centralized Nuclei.
Journal of neuromuscular diseasesSingle Intramuscular Injection of AAV-shRNA Reduces DNM2 and Prevents Myotubular Myopathy in Mice.
Molecular therapy : the journal of the American Society of Gene TherapyCongenital myopathies: disorders of excitation-contraction coupling and muscle contraction.
Nature reviews. NeurologyAllele-specific silencing therapy for Dynamin 2-related dominant centronuclear myopathy.
EMBO molecular medicineRYR1 causing distal myopathy.
Molecular genetics & genomic medicineA multicenter, retrospective medical record review of X-linked myotubular myopathy: The recensus study.
Muscle & nerve[Myonuclear domain and microtubule proteome during skeletal muscle maturation].
Medecine sciences : M/SDynamin-2-associated myopathy with electrical but not clinical myotonia.
Muscle & nerveDominant Centronuclear Myopathy with Early Childhood Onset due to a Novel Mutation in BIN1.
Journal of neuromuscular diseasesImpaired excitation-contraction coupling in muscle fibres from the dynamin2R465W mouse model of centronuclear myopathy.
The Journal of physiologyPhenotype variability and histopathological findings in patients with a novel DNM2 mutation.
Neuropathology : official journal of the Japanese Society of NeuropathologyExpression of the neuropathy-associated MTMR2 gene rescues MTM1-associated myopathy.
Human molecular geneticsDeficiency in Kelch protein Klhl31 causes congenital myopathy in mice.
The Journal of clinical investigationCommon and variable clinical, histological, and imaging findings of recessive RYR1-related centronuclear myopathy patients.
Neuromuscular disorders : NMDA rare case of centronuclear myopathy with DNM2 mutation: genotype-phenotype correlation.
Autopsy & case reportsAffected female carriers of MTM1 mutations display a wide spectrum of clinical and pathological involvement: delineating diagnostic clues.
Acta neuropathologicaDynamin-2 mutations linked to Centronuclear Myopathy impair actin-dependent trafficking in muscle cells.
Scientific reportsEmery-Dreifuss muscular dystrophy-linked genes and centronuclear myopathy-linked genes regulate myonuclear movement by distinct mechanisms.
Molecular biology of the cellInsights from genotype-phenotype correlations by novel SPEG mutations causing centronuclear myopathy.
Neuromuscular disorders : NMDGrand paternal inheritance of X-linked myotubular myopathy due to mosaicism, and identification of necklace fibers in an asymptomatic male.
Neuromuscular disorders : NMDLoss of Dynamin 2 GTPase function results in microcytic anaemia.
British journal of haematologyPhenotypes, genotypes, and prevalence of congenital myopathies older than 5 years in Denmark.
Neurology. GeneticsSarcolipin deletion exacerbates soleus muscle atrophy and weakness in phospholamban overexpressing mice.
PloS oneIn vivo imaging of skeletal muscle in mice highlights muscle defects in a model of myotubular myopathy.
IntravitalHereditary myopathies with early respiratory insufficiency in adults.
Muscle & nerveDihydropyridine receptor (DHPR, CACNA1S) congenital myopathy.
Acta neuropathologicaAbnormal spontaneous activity in primary myopathic disorders.
Muscle & nerveExome sequencing is a valuable approach in critically ill patients with suspected monogenic disease: Diagnosis of X-linked centronuclear myopathy in preterm twins.
Pediatrics and neonatologyProgressive Structural Defects in Canine Centronuclear Myopathy Indicate a Role for HACD1 in Maintaining Skeletal Muscle Membrane Systems.
The American journal of pathologyCalcium homeostasis alterations in a mouse model of the Dynamin 2-related centronuclear myopathy.
Biology openClinical, Electrophysiology, and Pathology Features of Dynamin Centronuclear Myopathy: A Case Report and Review of Literature.
Journal of clinical neuromuscular diseaseAssociações
Organizações que acompanham esta doença — pra ter apoio e orientação
Ainda não temos associações cadastradas para Miopatia centronuclear.
É de uma associação que acompanha esta doença? Fale com a gente →
Comunidades
Grupos ativos de quem convive com esta doença aqui no Raras
Ainda não existe comunidade no Raras para Miopatia centronuclear
Pacientes, familiares e cuidadores se organizam em comunidades pra compartilhar experiências, fazer perguntas e se apoiar. Você pode ser o primeiro.
Tire suas dúvidas
Perguntas, dicas e experiências compartilhadas aqui na página
Participe da discussão
Faça login para postar dúvidas, compartilhar experiências e interagir com especialistas.
Fazer loginDoenças relacionadas
Doenças com sintomas parecidos — ajudam quem ainda está buscando diagnóstico
Referências e fontes
Bases de dados externas citadas neste artigo
Publicações científicas
Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.
- Muscle-Specific DNM2 Overexpression Improves Charcot-Marie-Tooth Disease In Vivo and Reveals a Narrow Therapeutic Window in Skeletal Muscle.
- Incidence and Prevalence of Congenital Myopathies - A Population-Based Study From Western Sweden.
- Liver health in myotubular and centronuclear myopathies: a patient-driven data collection study to better understand liver health and improve standards of care.
- Integrative Multi-Omics and Network Analyses Reveal Pathogenic and Protective Pathways in Centronuclear Myopathies.
- Ca2+, ROS, IL-6, and p38 MAPK signaling loops underlying alterations in myotube formation induced by a severe MH/CCD mutation in RyR1.
- X-linked myotubular myopathy in a neonate: a case report and literature review.
- Polymorphic myopathological findings in a 77-year-old woman with oculo-bulbo-facial and distal weakness.
- Tamoxifen treatment fails to improve muscle dysfunction in a model of recessive RYR1-linked centronuclear myopathy.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:595(Orphanet)
- MONDO:0018947(MONDO)
- GARD:101(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Busca completa no PubMed(PubMed)
- Q782958(Wikidata)
Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar
