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
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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
- 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.
- 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.
- STAC3 variants cause a congenital myopathy with distinctive dysmorphic features and malignant hyperthermia susceptibility(2018) ZAHARIEVA, Irina T.; SARKOZY, Anna; MUNOT, Pinki; MANZUR, Adnan; O'GRADY, Gina; RENDU, John; MALFATTI, Eduardo; AMTHOR, Helge; SERVAIS, Laurent; URTIZBEREA, J. Andoni; ABATH NETO, Osorio; ZANOTELI, Edmar; DONKERVOORT, Sandra; TAYLOR, Juliet; DIXON, Joanne; POKE, Gemma; FOLEY, A. Reghan; HOLMES, Chris; WILLIAMS, Glyn; HOLDER, Muriel; YUM, Sabrina; MEDNE, Livija; QUIJANO-ROY, Susana; ROMERO, Norma B.; FAURE, Julien; FENG, Lucy; BASTAKI, Laila; DAVIS, Mark R.; PHADKE, Rahul; SEWRY, Caroline A.; BONNEMANN, Carsten G.; JUNGBLUTH, Heinz; BACHMANN, Christoph; TREVES, Susan; MUNTONI, FrancescoSH3 and cysteine-rich domain-containing protein 3 (STAC3) is an essential component of the skeletal muscle excitation-contraction coupling (ECC) machinery, though its role and function are not yet completely understood. Here, we report 18 patients carrying a homozygous p.(Trp284Ser) STAC3 variant in addition to a patient compound heterozygous for the p.(Trp284Ser) and a novel splice site change (c.997-1G > T). Clinical severity ranged from prenatal onset with severe features at birth, to a milder and slowly progressive congenital myopathy phenotype. A malignant hyperthermia (MH)-like reaction had occurred in several patients. The functional analysis demonstrated impaired ECC. In particular, KCl-induced membrane depolarization resulted in significantly reduced sarcoplasmic reticulum Ca2+ release. Co-immunoprecipitation of STAC3 with Ca(V)1.1 in patients and control muscle samples showed that the protein interaction between STAC3 and Ca(V)1.1 was not significantly affected by the STAC3 variants. This study demonstrates that STAC3 gene analysis should be included in the diagnostic work up of patients of any ethnicity presenting with congenital myopathy, in particular if a history of MH-like episodes is reported. While the precise pathomechanism remains to be elucidated, our functional characterization of STAC3 variants revealed that defective ECC is not a result of Ca(V)1.1 sarcolemma mislocalization or impaired STAC3-Ca(V)1.1 interaction.
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