FERNANDO KOK
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Neurologia, Faculdade de Medicina - Docente
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/15 - Laboratório de Investigação em Neurologia, Hospital das Clínicas, Faculdade de Medicina
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/15 - Laboratório de Investigação em Neurologia, Hospital das Clínicas, Faculdade de Medicina
8 resultados
Resultados de Busca
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conferenceObject Moesin (MSN) Mutation Leading to Primary Immunodeficiency: Case Report(2017) TEIXEIRA, J. V. S.; ALMEIDA, S. K. A.; PIRES, L.; KOK, F.; GRUMACH, A. S.- Clinical and genetic characterization of leukoencephalopathies in adults(2017) LYNCH, David S.; PAIVA, Anderson Rodrigues Brandao de; ZHANG, Wei Jia; BUGIARDINI, Enrico; FREUA, Fernando; LUCATO, Leandro Tavares; MACEDO-SOUZA, Lucia Ines; LAKSHMANAN, Rahul; KINSELLA, Justin A.; MERWICK, Aine; ROSSOR, Alexander M.; BAJAJ, Nin; HERRON, Brian; MCMONAGLE, Paul; MORRISON, Patrick J.; HUGHES, Deborah; PITTMAN, Alan; LAURA, Matilde; REILLY, Mary M.; WARREN, Jason D.; MUMMERY, Catherine J.; SCHOTT, Jonathan M.; ADAMS, Matthew; FOX, Nick C.; MURPHY, Elaine; DAVAGNANAM, Indran; KOK, Fernando; CHATAWAY, Jeremy; HOULDEN, HenryLeukodystrophies and genetic leukoencephalopathies are a rare group of disorders leading to progressive degeneration of cerebral white matter. They are associated with a spectrum of clinical phenotypes dominated by dementia, psychiatric changes, movement disorders and upper motor neuron signs. Mutations in at least 60 genes can lead to leukoencephalopathy with often overlapping clinical and radiological presentations. For these reasons, patients with genetic leukoencephalopathies often endure a long diagnostic odyssey before receiving a definitive diagnosis or may receive no diagnosis at all. In this study, we used focused and whole exome sequencing to evaluate a cohort of undiagnosed adult patients referred to a specialist leukoencephalopathy service. In total, 100 patients were evaluated using focused exome sequencing of 6100 genes. We detected pathogenic or likely pathogenic variants in 26 cases. The most frequently mutated genes were NOTCH3, EIF2B5, AARS2 and CSF1R. We then carried out whole exome sequencing on the remaining negative cases including four family trios, but could not identify any further potentially disease-causing mutations, confirming the equivalence of focused and whole exome sequencing in the diagnosis of genetic leukoencephalopathies. Here we provide an overview of the clinical and genetic features of these disorders in adults.
conferenceObject CHARCOT-MARIE-TOOTH 2W. A NEW MUTATION?(2017) FREITAS, M. de; DIAS, J.; VIDAL, C.; SZKLARZ, D.; NASCIMENTO, O.; KOK, F.- Teaching Video NeuroImages: Spinocerebellar ataxia type 3 presenting with a cock-walk gait phenotype(2017) ROCHA, Eva; VALE, Thiago Cardoso; KOK, Fernando; PEDROSO, Jose Luiz; BARSOTTINI, Orlando G.
- High phenotypic variability in Gerstmann-Straussler-Scheinker disease(2017) SMID, Jerusa; NETO, Adalberto Studart; LANDEMBERGER, Michele Christine; MACHADO, Cleiton Fagundes; NOBREGA, Paulo Ribeiro; CANEDO, Nathalie Henriques Silva; SCHULTZ, Rodrigo Rizek; NASLAVSKY, Michel Satya; ROSEMBERG, Sergio; KOK, Fernando; CHIMELLI, Leila; MARTINS, Vilma Regina; NITRINI, RicardoGerstmann-Straussler-Scheinker is a genetic prion disease and the most common mutation is p.Pro102Leu. We report clinical, molecular and neuropathological data of seven individuals, belonging to two unrelated Brazilian kindreds, carrying the p.Pro102Leu. Marked differences among patients were observed regarding age at onset, disease duration and clinical presentation. In the first kindred, two patients had rapidly progressive dementia and three exhibited predominantly ataxic phenotypes with variable ages of onset and disease duration. In this family, age at disease onset in the mother and daughter differed by 39 years. In the second kindred, different phenotypes were also reported and earlier ages of onset were associated with 129 heterozygosis. No differences were associated with apoE genotype. In these kindreds, the codon 129 polymorphism could not explain the clinical variability and 129 heterozygosis was associated with earlier disease onset. Neuropathological examination in two patients confirmed the presence of typical plaques and PrPsc immunopositivity.
- Santos syndrome is caused by mutation in the WNT7A gene(2017) ALVES, Leandro U.; SANTOS, Silvana; MUSSO, Camila M.; EZQUINA, Suzana A. M.; OPITZ, John M.; KOK, Fernando; OTTO, Paulo A.; MINGRONI-NETTO, Regina C.We have recently described a family with a condition (Santos syndrome (SS; MIM 613005)) characterized by fibular agenesis/ hypoplasia, hypoplastic femora and grossly malformed/deformed clubfeet with severe oligodactyly, ungual hypoplasia/anonychia, sometimes associated with mild brachydactyly and occasional pre-axial polydactyly. Autosomal dominant inheritance with incomplete penetrance was suggested, but autosomal recessive inheritance could not be ruled out, due to the high frequency of consanguineous matings in the region where the family lived. This report deals with linkage studies and exome sequencing, disclosing a novel variant in WNT7A, c. 934G4A (p. Gly312Ser), as the cause of this syndrome. This variant was present in homozygous state in five individuals typically affected by the SS syndrome, and in heterozygous state in the son of one affected homozygous individual. The heterozygous boy presented only unilateral complex polysyndactyly and we hypothesize that he either presents a distinct defect or that his phenotype results from a rare, mild clinical manifestation of the variant in heterozygous state. Variants in WNT7A are known to cause at least two other limb defect disorders, the syndromes of Fuhrmann and Al-Awadi/ Raas-Rothschild. Despite their variable degree of expressivity and overlap, the three related conditions can be differentiated phenotypically in most instances.
- Biallelic mutation in FDXIL leads to a complex phenotype: optic atrophy, reversible leukoencephalopathy, metabolic myopathy and axonal polyneuropathy(2017) GURGEL-GIANNETTI, J.; LYNCH, D.; PAIVA, A.; YAMAMOTO, G.; LUCATO, L.; AMORIM, S.; FREUA, F.; GIANNETTI, A.; RIPA, B.; MONTI, F.; RIBEIRO, M.; KNAAP, M. Van der; OLDFORS, A.; VAINZOF, M.; HOLDEN, H.; KOK, F.
conferenceObject Clinical and genetic characterisation of adult onset leukoencephalopathy(2017) LYNCH, David; PAIVA, Anderson Rodrigues Brandao de; ZHANG, Wei Jia; LAKSHMANAN, Rahul; DAVAGNANAM, Indran; FOX, Nick; MURPHY, Elaine; KOK, Fernando; CHATAWAY, Jeremy; HOULDEN, Henry