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
5 resultados
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- 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
- 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.
- 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.
article 8 Citação(ões) na Scopus Nonlethal CHRNA1-Related Congenital Myasthenic Syndrome with a Homozygous Null Mutation(2017) ABATH NETO, Osorio; HEISE, Carlos Otto; MORENO, Cristiane de Araujo Martins; ESTEPHAN, Eduardo de Paula; MESROB, Lilia; LECHNER, Doris; BOLAND, Anne; DELEUZE, Jean-Francois; OLIVEIRA, Acary Souza Bulle; REED, Umbertina Conti; BIANCALANA, Valerie; LAPORTE, Jocelyn; ZANOTELI, Edmar