OSORIO LOPES ABATH NETO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
19 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 19
- Desmin-associated myofibrillar myopathy with cap-like structures in the muscle biopsy(2016) SILVA, A.; ESTEPHAN, E.; MORENO, C.; MENDONCA, R.; NISHIMURA, P.; GALINDO, L.; CARVALHO, M.; ABATH-NETO, O.; ZANOTELI, E.
- Muscle biopsy with dystrophic pattern and rimmed vacuoles: GNE myopathy in a Brazilian patient(2017) ESTEPHAN, Eduardo de Paula; MORENO, Cristiane Araujo Martins; SILVA, Andre Macedo Serafim da; MENDONCA, Rodrigo de Holanda; ABATH NETO, Osorio; NISHIMURA, Patricia Yoshi; GALINDO, Layla Testa; ZANOTELI, Edmar
- One family, one gene and three phenotypes: A novel VCP (valosin-containing protein) mutation associated with myopathy with rimmed vacuoles, amyotrophic lateral sclerosis and frontotemporal dementia(2016) ABRAHAO, Agessandro; NETO, Osorio Abath; KOK, Fernando; ZANOTELI, Edmar; SANTOS, Bibiana; PINTO, Wladimir Bocca Vieira de Rezende; BARSOTTINI, Orlando Graziani Povoas; OLIVEIRA, Acary Souza Bulle; PEDROSO, Jose LuizBackground: VCP (valosin-containing protein gene) variants have been associated with peripheral and central neurodegenerative processes, including inclusion body myopathy (IBM), Paget disease of bone (PDB), frontotemporal dementia (FTD), and familial amyotrophic lateral sclerosis (ALS) type 14. The combination of IBM, PDB (IBMPFD1) can presented in one individual. However, the association of IBMPFD1 and ALS in the same family is rare. Methods: We reported three individuals from a Brazilian kindred with intrafamilial phenotype variability. Whole exome sequencing (WES) of the proband was performed and revealed a novel VCP variant. VCP Sanger sequencing was performed in the proband and his family members to confirm WES finding and segregation. We performed a systematic review of the literature regarding the genotypic-phenotypic VCP correlations. Results: Each individual presented with either myopathy with rimmed vacuoles, ALS, or FTD. There was no PDB. WES of the proband identified the heterozygous variant c.271A> T (p.Asn91Tyr) in the exon 3 of VCP. Sanger sequencing confirmed the segregation of this variant in an autosomal-dominant pattern. Conclusion: This study expands the genotypic spectrum of the missense mutations of the VCP gene with a novel p.Asn9lTyr variant found in a Brazilian family presenting with the unusual intrafamiliar association of myopathy with rimmed vacuoles, ALS and FTD.
- Necklace fibers as histopathological marker in a patient with severe form of X-linked myotubular myopathy(2012) GURGEL-GIANNETTI, Juliana; ZANOTELI, Edmar; CONCENTINO, Eralda Luiza de Castro; ABATH NETO, Osorio; PESQUERO, Joao Bosco; REED, Umbertina Conti; VAINZOF, MarizX-linked myotubular myopathy due to mutations in the MTM1 gene is classically characterized by a severe neonatal phenotype and a typical muscle biopsy presenting globular and centrally located nuclei in muscle myofibers. Recently, four patients with mild late-onset form have been described, a male with a hemizygous mutation and three females with heterozygous mutations in the MTM1 gene. The muscle biopsies were performed at 13-35 years of age and a new histological marker, the necklace fibers, was described. Here, we report two siblings with the pathogenic c.664 C > T mutation in the MTM1 gene, presenting a severe muscle weakness and respiratory impairment requiring ventilatory support since the first months of life until death, at the age of 36 months and 5 months. In the older brother the muscle biopsy, performed at the age of 30 months, showed almost 100% of necklace fibers, which were not present in the younger one submitted to muscle biopsy at 5 months of age. Our findings confirm the necklace fibers can be a histopathological finding of MTM1 myopathies, even in the severe neonatal form, and suggest that the necklace fibers appear or increase in number over time.
- Clinical aspects of patients with sarcoglycanopathies under steroids therapy(2014) ALBUQUERQUE, Marco A. V.; ABATH-NETO, Osorio; MAXIMINO, Jessica R.; CHADI, Gerson; ZANOTELI, Edmar; REED, Umbertina C.Patients with sarcoglycanopathies, which comprise four subtypes of autosomal recessive limb-girdle muscular dystrophies, usually present with progressive weakness leading to early loss of ambulation and premature death, and no effective treatment is currently available. Objective: To present clinical aspects and outcomes of six children with sarcoglycanopathies treated with steroids for at least one year. Method: Patient files were retrospectively analyzed for steroid use. Results: Stabilization of muscle strength was noted in one patient, a slight improvement in two, and a slight worsening in three. In addition, variable responses of forced vital capacity and cardiac function were observed. Conclusions: No overt clinical improvement was observed in patients with sarcoglycanopathies under steroid therapy. Prospective controlled studies including a larger number of patients are necessary to determine the effects of steroids for sarcoglycanopathies.
- Common and variable clinical, histological, and imaging findings of recessive RYR1-related centronuclear myopathy patients(2017) NETO, Osorio Abath; MORENO, Cristiane de Araujo Martins; MALFATTI, Edoardo; DONKERVOORT, Sandra; BOHM, Johann; GUIMARAES, Julio Brandao; FOLEY, A. Reghan; MOHASSEL, Payam; DASTGIR, Jahannaz; BHARUCHA-GOEBEL, Diana Xerxes; MONGES, Soledad; LUBIENIECKI, Fabiana; COLLINS, James; MEDNE, Livija; SANTI, Mariarita; YUM, Sabrina; BANWELL, Brenda; SALORT-CAMPANA, Emmanuelle; RENDU, John; FAURE, Julien; YIS, Uluc; EYMARD, Bruno; CHERAUD, Chrystel; SCHNEIDER, Raphael; THOMPSON, Julie; LORNAGE, Xaviere; MESROB, Lilia; LECHNER, Doris; BOLAND, Anne; DELEUZE, Jean-Francois; REED, Umbertina Conti; OLIVEIRA, Acary Souza Bulle; BIANCALANA, Valerie; ROMERO, Norma B.; BONNEMANN, Carsten G.; LAPORTE, Jocelyn; ZANOTELI, EdmarMutations in RYR1 give rise to diverse skeletal muscle phenotypes, ranging from classical central core disease to susceptibility to malignant hyperthermia. Next-generation sequencing has recently shown that RYR1 is implicated in a wide variety of additional myopathies, including centronuclear myopathy. In this work, we established an international cohort of 21 patients from 18 families with autosomal recessive RYR1-related centronuclear myopathy, to better define the clinical, imaging, and histological spectrum of this disorder. Early onset of symptoms with hypotonia, motor developmental delay, proximal muscle weakness, and a stable course were common clinical features in the cohort. Ptosis and/or ophthalmoparesis, facial weakness, thoracic deformities, and spinal involvement were also frequent but variable. A common imaging pattern consisted of selective involvement of the vastus lateralis, adductor magnus, and biceps brachii in Comparison to adjacent muscles. In addition to a variable prominence of central nuclei, muscle biopsy from 20 patients showed type 1 fiber predominance and a wide range of intermyofibrillary architecture abnormalities. All families harbored compound heterozygous mutations, most commonly a truncating mutation combined with a missense mutation. This work expands the phenotypic characterization of patients with recessive RYR1-related centronuclear myopathy by highlighting common and variable clinical, histological, and imaging findings in these patients.
- A common CHRNE mutation in Brazilian patients with congenital myasthenic syndrome(2018) ESTEPHAN, Eduardo de Paula; SOBREIRA, Claudia Ferreira da Rosa; SANTOS, Andre Cleriston Jose dos; TOMASELLI, Pedro Jose; MARQUES JR., Wilson; ORTEGA, Roberta Paiva Magalhes; COSTA, Marcela Camara Machado; SILVA, Andre Macedo Serafim da; MENDONCA, Rodrigo Holanda; CALDAS, Vitor Marques; ZAMBON, Antonio Alberto; ABATH NETO, Osorio; MARCHIORI, Paulo Euripedes; HEISE, Carlos Otto; REED, Umbertina Conti; AZUMA, Yoshiteru; TOPF, Ana; LOCHMULLER, Hanns; ZANOTELI, EdmarThe most common causes of congenital myasthenic syndromes (CMS) are CHRNE mutations, and some pathogenic allelic variants in this gene are especially frequent in certain ethnic groups. In the southern region of Brazil, a study found the c.130dupG CHRNE mutation in up to 33% of families with CMS. Here, we aimed to verify the frequency of this mutation among individuals with CMS in a larger cohort of CMS patients from different areas of Brazil and to characterize clinical features of these patients. Eighty-four patients with CMS, from 72 families, were clinically evaluated and submitted to direct sequencing of the exon 2 of CHRNE. The c.130dupG mutation was found in 32 patients (23 families), with 26 patients (19 families, 26.3%) in homozygosis, confirming its high prevalence in different regions of Brazil. Among the homozygous patients, the following characteristics were frequent: onset of symptoms before 2 years of age (92.3%), little functional restriction (92.3%), fluctuating symptoms (100%), ocular muscle impairment (96.1%), ptosis (100%), limb weakness (88.4%), response to pyridostigmine (100%), facial involvement (77%), and bulbar symptoms (70.8%). The pretest probability of finding at least one allele harbouring the c.130dupG mutation was 38.1%. Selecting only patients with impaired eye movement together with limb weakness and improvement with pyridostigmine, the probability increases to 72.2%. This clinical pre-selection of patients is likely a useful tool for regions where CHRNE mutations have a founder effect. In conclusion, the CHRNE mutation c.130dupG leads to fairly benign natural course of the disease with relative homogeneity.
- Affected female carriers of MTM1 mutations display a wide spectrum of clinical and pathological involvement: delineating diagnostic clues(2017) BIANCALANA, Valerie; SCHEIDECKER, Sophie; MIGUET, Marguerite; LAQUERRIERE, Annie; ROMERO, Norma B.; STOJKOVIC, Tanya; NETO, Osorio Abath; MERCIER, Sandra; VOERMANS, Nicol; TANNER, Laura; ROGERS, Curtis; OLLAGNON-ROMAN, Elisabeth; ROPER, Helen; BOUTTE, Celia; BEN-SHACHAR, Shay; LORNAGE, Xaviere; VASLI, Nasim; SCHAEFER, Elise; LAFORET, Pascal; POUGET, Jean; MOERMAN, Alexandre; PASQUIER, Laurent; MARCORELLE, Pascale; MAGOT, Armelle; KUSTERS, Benno; STREICHENBERGER, Nathalie; TRANCHANT, Christine; DONDAINE, Nicolas; SCHNEIDER, Raphael; GASNIER, Claire; CALMELS, Nadege; KREMER, Valerie; NGUYEN, Karine; PERRIER, Julie; KAMSTEEG, Erik Jan; CARLIER, Pierre; CARLIER, Robert-Yves; THOMPSON, Julie; BOLAND, Anne; DELEUZE, Jean-Francois; FARDEAU, Michel; ZANOTELI, Edmar; EYMARD, Bruno; LAPORTE, JocelynX-linked myotubular myopathy (XLMTM), a severe congenital myopathy, is caused by mutations in the MTM1 gene located on the X chromosome. A majority of affected males die in the early postnatal period, whereas female carriers are believed to be usually asymptomatic. Nevertheless, several affected females have been reported. To assess the phenotypic and pathological spectra of carrier females and to delineate diagnostic clues, we characterized 17 new unrelated affected females and performed a detailed comparison with previously reported cases at the clinical, muscle imaging, histological, ultrastructural and molecular levels. Taken together, the analysis of this large cohort of 43 cases highlights a wide spectrum of clinical severity ranging from severe neonatal and generalized weakness, similar to XLMTM male, to milder adult forms. Several females show a decline in respiratory function. Asymmetric weakness is a noteworthy frequent specific feature potentially correlated to an increased prevalence of highly skewed X inactivation. Asymmetry of growth was also noted. Other diagnostic clues include facial weakness, ptosis and ophthalmoplegia, skeletal and joint abnormalities, and histopathological signs that are hallmarks of centronuclear myopathy such as centralized nuclei and necklace fibers. The histopathological findings also demonstrate a general disorganization of muscle structure in addition to these specific hallmarks. Thus, MTM1 mutations in carrier females define a specific myopathy, which may be independent of the presence of an XLMTM male in the family. As several of the reported affected females carry large heterozygous MTM1 deletions not detectable by Sanger sequencing, and as milder phenotypes present as adult-onset limb-girdle myopathy, the prevalence of this myopathy is likely to be greatly underestimated. This report should aid diagnosis and thus the clinical management and genetic counseling of MTM1 carrier females. Furthermore, the clinical and pathological history of this cohort may be useful for therapeutic projects in males with XLMTM, as it illustrates the spectrum of possible evolution of the disease in patients surviving long term.
- Clinical and Histologic Findings in ACTA1-Related Nemaline Myopathy: Case Series and Review of the Literature(2017) MORENO, Cristiane de Araujo Martins; NETO, Osorio Abath; DONKERVOORT, Sandra; HU, Ying; REED, Umbertina Conti; OLIVEIRA, Acary Sousa Bulle; BONNEMANN, Carsten; ZANOTELI, EdmarBACKGROUND: Nemaline myopathy is a rare congenital disease of skeletal muscle characterized by muscle weakness and hypotonia, as well as the diagnostic presence of nemaline rods in skeletal muscle fibers. Nemaline myopathy is genetically and phenotypically heterogeneous and, so far, mutations in 11 different genes have been associated with this disease. Dominant mutations in ACTA1 are the second most frequent genetic cause of nemaline myopathy and can lead to a variety of clinical and histologic phenotypes. PATIENTS AND METHODS: We present a series of ACTA1-related cases from a Brazilian cohort of 23 patients with nemaline myopathy, diagnosed after Sanger sequencing the entire coding region of ACTA1, and review the literature on ACTA1-related nemaline myopathy. RESULTS: The study confirmed ACTAI mutations in four patients, including one with intranuclear rods, one with large intracytoplasmic aggregates, and two with nemaline intracytoplasmic rods. A repeat muscle biopsy in one patient did not show histological progression. CONCLUSION: Despite the recognized phenotypic variability in ACTA1-related nemaline myopathy, clinical and histological presentations appear to correlate with the position of the mutation, which confirms emerging genotype/phenotype correlations and better predict the prognosis of affected patients.
- Recessive congenital fiber type disproportion caused by TPM3 mutation(2018) MORENO, C.; ESTEPHAN, E.; ABATH NETO, O.; CAMELO, C.; SILVA, A.; REED, U.; BONNEMANN, C.; ZANOTELI, E.