ANDRE MACEDO SERAFIM DA SILVA
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
4 resultados
Resultados de Busca
Agora exibindo 1 - 4 de 4
- Severe brain involvement in 5q spinal muscular atrophy type 0(2019) MENDONCA, Rodrigo H.; ROCHA, Antonio J.; LOZANO-ARANGO, Andres; DIAZ, Astry B.; CASTIGLIONI, Claudia; SILVA, Andre M. S.; REED, Umbertina C.; KULIKOWSKI, Leslie; PARAMONOV, Ida; CUSCO, Ivon; TIZZANO, Eduardo F.; ZANOTELI, EdmarSpinal muscular atrophy (SMA) type 0 is the most severe form of SMA, associated with the SMN1 gene and manifesting at birth. Most patients die in the first weeks of life. In this work, we present 3 patients with SMA type 0 who survived >1 year and presented diffuse and progressive brain abnormalities on magnetic resonance imaging, which are not usually seen in patients with SMA. Thus, severe brain involvement may likely be the full end manifestation of an already extreme SMA phenotype caused by substantial reduction of the SMN protein in the brain. ANN NEUROL 2019
- The Location of Disease-Causing DES Variants Determines the Severity of Phenotype and the Morphology of Sarcoplasmic Aggregates(2022) SILVA, Andre Macedo Serafim; RODRIGO, Patricia; MORENO, Cristiane Araujo Martins; MENDONCA, Rodrigo de Holanda; ESTEPHAN, Eduardo de Paula; CAMELO, Clara Gontijo; CAMPOS, Eliene Dutra; DIAS, Alexandre Torchio; NASCIMENTO, Amom Mendes; KULIKOWSKI, Leslie Domenici; OLIVEIRA, Acary Souza Bulle; REED, Umbertina Conti; GOLDFARB, Lev G.; OLIVE, Montse; ZANOTELI, EdmarDesmin (DES) is the main intermediate muscle filament that connects myofibrils individually and with the nucleus, sarcolemma, and organelles. Pathogenic variants of DES cause desminopathy, a disorder affecting the heart and skeletal muscles. We aimed to analyze the clinical features, morphology, and distribution of desmin aggregates in skeletal muscle biopsies of patients with desminopathy and to correlate these findings with the type and location of disease-causing DES variants. This retrospective study included 30 patients from 20 families with molecularly confirmed desminopathy from 2 neuromuscular referral centers. We identified 2 distinct patterns of desmin aggregates: well-demarcated subsarcolemmal aggregates and diffuse aggregates with poorly delimited borders. Pathogenic variants located in the 1B segment and the tail domain of the desmin molecule are more likely to present with early-onset cardiomyopathy compared to patients with variants in other segments. All patients with mutations in the 1B segment had well-demarcated subsarcolemmal aggregates, but none of the patients with variants in other desmin segments showed such histological features. We suggest that variants located in the 1B segment lead to well-shaped subsarcolemmal desmin aggregation and cause disease with more frequent cardiac manifestations. These findings will facilitate early identification of patients with potentially severe cardiac syndromes.
- Reply to ""Global Central Nervous System Atrophy in Spinal Muscular Atrophy Type 0""(2019) MENDONCA, Rodrigo H.; ROCHA, Antonio J.; LOZANO-ARANGO, Andres; DIAZ, Astry B.; CASTIGLIONI, Claudia; SILVA, Andre M. S.; REED, Umbertina C.; KULIKOWSKI, Leslie; PARAMONOV, Ida; CUSCO, Ivon; TIZZANO, Eduardo F.; ZANOTELI, Edmar
- Congenital myasthenic syndrome: Correlation between clinical features and molecular diagnosis(2022) ESTEPHAN, Eduardo P.; ZAMBON, Antonio A.; THOMPSON, Rachel; POLAVARAPU, Kiran; JOMAA, Danny; TOPF, Ana; HELITO, Paulo V. P.; HEISE, Carlos O.; MORENO, Cristiane A. M.; SILVA, Andre M. S.; KOUYOUMDJIAN, Joao A.; MORITA, Maria da Penha; REED, Umbertina C.; LOCHMULLER, Hanns; ZANOTELI, EdmarObjectives To present phenotype features of a large cohort of congenital myasthenic syndromes (CMS) and correlate them with their molecular diagnosis. Methods Suspected CMS patients were divided into three groups: group A (limb, bulbar or axial weakness, with or without ocular impairment, and all the following: clinical fatigability, electrophysiology compatible with neuromuscular junction involvement and anticholinesterase agents response), group B (limb, bulbar or axial weakness, with or without ocular impairment, and at least one of additional characteristics noted in group A) and group C (pure ocular syndrome). Individual clinical findings and the clinical groups were compared between the group with a confirmed molecular diagnosis of CMS and the group without molecular diagnosis or with a non-CMS molecular diagnosis. Results Seventy-nine patients (68 families) were included in the cohort: 48 in group A, 23 in group B and 8 in group C. Fifty-one were considered confirmed CMS (30 CHRNE, 5 RAPSN, 4 COL13A1, 3 DOK7, 3 COLQ, 2 GFPT1, 1 CHAT, 1 SCN4A, 1 GMPPB, 1 CHRNA1), 7 probable CMS, 5 non-CMS and 16 unsolved. The chance of a confirmed molecular diagnosis of CMS was significantly higher for group A and lower for group C. Some individual clinical features, alterations on biopsy and electrophysiology enhanced specificity for CMS. Muscle imaging showed at least mild alterations in the majority of confirmed cases, with preferential involvement of soleus, especially in CHRNE CMS. Conclusions Stricter clinical criteria increase the chance of confirming a CMS diagnosis, but may lose sensitivity, especially for some specific genes.