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- ItemAcesso aberto (Open Access)Caracterização clínica, epidemiológica, neurorradiológica e genética de pacientes com síndrome Fosmn(Universidade Federal de São Paulo (UNIFESP), 2018-07-26) Pinto, Wladimir Bocca Vieira de Rezende [UNIFESP]; Oliveira, Acary Souza Bulle [UNIFESP]; http://lattes.cnpq.br/3911841387107665; http://lattes.cnpq.br/8416591409563935; Universidade Federal de São Paulo (UNIFESP)Objectives: Perform clinical characterization of motor and nonmotor aspects of FOSMN (facialonset sensory and motor neuronopathy) syndrome in Brazilian patients. Secondary objectives included: (i) evaluation of the genetic basis associated with FOSMN syndrome, especially in patients with familial history of MND (Motor Neuron Disease)/ALS (Amyotrophic Lateral Sclerosis) or other neurodegenerative diseases or a specific genetic spectrum; (ii) discussion of the main pathophysiological mechanisms involved with FOSMN syndrome correlating genetic findings observed in sporadic and familial MND/ALS and the main atypical variants. Methods: A retrospective clinical study was performed and a wide evaluation and review of clinical, laboratorial, neurophysiological and neurogenetic findings from ten nonrelated Brazilian patients with FOSMN syndrome selected from a group of 900 patients followedup from January 2012 and December 2016 in MND/ALS Unit, Division of Neuromuscular Diseases, Federal University of São Paulo (UNIFESP), São Paulo, Brazil. Medical records were verified including clinical characterization of signs and symptoms of motor and nonmotor compromise (including basic cognitive profile), laboratorial evaluation, neuroimaging studies and specific genetic exams. Genetic studies were reviewed and performed in cases with previously established or suggestive familial (or hereditary) context of a specific neurodegenerative phenotype of familial MND/ALS. Results: Mean age at onset of symptoms was at 52.1 years, with equal involvement of men and women. Patients presented with hemifacial paraesthesia (including oral cavity mucosa) or bialteral paraesthesia and weakness in the face, evolving with dysphagia, dysphonia and amyotrophy in the face and tongue, eventually with compromise of other bulbar and pontine cranial nerves, and finally at latestages with dropped head syndrome, weakness in the upper limbs and sensory changes in the upper limbs in a similar pattern to syryngomyelialike. Eight patients presented with multidomain cognitive compromise, half of them with cortical brain atrophy and none of them with spontaneous cognitive or behavioral complaints. All patients had diffuse chronic denervation involving the bulbar, cervical and thoracic myotomes (most of them also with acute denervation) and abnormal testing of the blink reflex. Positive family history of neurodegeneration was identified in six cases, disclosing monogenic pathogenic variants in three families (VCP, TARDBP and CHCHD10 genes). The worst clinical prognosis regarding mortality and severe motor handicap was observed in one single case with early bulbaronset of symptoms and high tendency of early cervical weakness (droppedhead syndrome). Conclusion: This case series has demonstrated new clinical and neurogenetic findings associated with FOSMN syndrome: (i) motor clinical course is not always benign with worse prognosis associated with “droppedhead” syndrome and early bulbar compromise; (ii) although considered a sporadic MND in current literature, FOSMN syndrome may be part of a complex familial neurodegenerative spectrum; (iii) it has been observed the association of FOSMN syndrome in three patients with pathogenic variants in TARDBP, VCP and CHCHD10 genes; (iv) cognitive compromise may be underdiagnosed in cases of FOSMN syndrome possibly due to subclinical involvement.
- ItemSomente MetadadadosDetection of Spinal Muscular Atrophy Carriers in a Sample of the Brazilian Population(Karger, 2011-01-01) Bueno, K. C.; Gouvea, S. P.; Genari, A. B.; Funayama, C. A.; Zanette, D. L.; Silva, W. A.; Oliveira, A. B. [UNIFESP]; Scola, R. H.; Werneck, L. C.; Marques, W.; Universidade de São Paulo (USP); Univ Fed Parana; Universidade Federal de São Paulo (UNIFESP)Background: Spinal muscular atrophy is a common autosomal recessive neuromuscular disorder caused by mutations in the SMN1 gene. Identification of spinal muscular atrophy carriers has important implications for individuals with a family history of the disorder and for genetic counseling. the aim of this study was to determine the frequency of carriers in a sample of the nonconsanguineous Brazilian population by denaturing high-performance liquid chromatography (DHPLC). Methods: To validate the method, we initially determined the relative quantification of DHPLC in 28 affected patients (DHPLC values: 0.00) and 65 parents (DHPLC values: 0.49-0.69). Following quantification, we studied 150 unrelated nonconsanguineous healthy individuals from the general population. Results: Four of the 150 healthy individuals tested (with no family history of a neuromuscular disorder) presented a DHPLC value in the range of heterozygous carriers (0.6-0.68). Conclusions: Based on these results, we estimated there is a carrier frequency of 2.7% in the nonconsanguineous Brazilian population, which is very similar to other areas of the world where consanguineous marriage is not common. This should be considered in the process of genetic counseling and risk calculations. Copyright (C) 2011 S. Karger AG, Basel
- ItemSomente MetadadadosSpinal muscular atrophy due to a de novo 1.3 Mb deletion: Implication for genetic counseling(Elsevier B.V., 2013-05-01) Jacy da Silva, Luciana Rodrigues [UNIFESP]; Stephano Colovati, Mileny Esbravatti [UNIFESP]; Coprerski, Bruno [UNIFESP]; Fernandez de Andrade, Carlos Eugenio; Zanoteli, Edmar; Raskin, Salmo; Oliveira, Mariana Moyses [UNIFESP]; Melaragno, Maria Isabel [UNIFESP]; Alvarez Perez, Ana Beatriz [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Santa Marcelina Hosp; Universidade de São Paulo (USP); GenetikaWe report a 3-year-old female with type I spinal muscular atrophy (SMA) born to a young and non-consanguineous couple. the child presented at two months of life with intense muscle weakness affecting predominantly proximal portions of the limbs, especially the legs, muscle hypotonia, fasciculation of the tongue, and severe respiratory muscle involvement. She remained in an intensive care unit with an assisted ventilation system from the fourth month of life. She died at 3 years of age from pulmonary infection. Molecular analysis confirmed the diagnosis of SMA but revealed that only the father was an asymptomatic carrier. Because SMN1 is mapped in a complex region containing repetitive elements due to an inverted duplication of approximately 500 kb, we carry out an SNP array and detected a 1.3 Mb deletion including the SMN1 and SMN2 genes that explain the disease. (C) 2013 Elsevier B.V. All rights reserved.