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
35 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 35
- Defects in iron-sulphur cluster assembly proteins ISCU and FDX2 cause characteristic mitochondrial myopathy(2019) THOMSEN, C.; GURGEL-GIANNETTI, J.; SUNNERHAGEN, Y.; GIANNETTI, A.; KOK, F.; VAINZOF, M.; OLDFORS, A.
conferenceObject Hypomyelinating Leukodystrophy: Clinical, Electrophysiological and Neuroimaging Characterization(2012) FREITAS, M. R.; KOK, F.; BRENNER, C.; LEITE, C. C.; GARZON, E.; MANGINI, N. N.; AMORIM, S.- A case of mitochondrial DNA depletion syndrome type 11-expanding the genotype and phenotype(2023) ROCHA, Emanuelle Bianchi da Silva; RODRIGUES, Ketteny de Lima; MONTOURO, Laura Alonso Matheus; COELHO, erica Nogueira; KOUYOUMDJIAN, Joao Aris; KOK, Fernando; NOBREGA, Paulo Ribeiro; GRACA, Carla Renata; MORITA, Maria da Penha Ananias; ESTEPHAN, Eduardo de PaulaMitochondrial DNA depletion syndrome type 11 (MTDPS11) is caused by pathogenic variants in MGME1 gene. We report a woman, 40-year-old, who presented slow progressive drop eyelid at 11-year old with, learning difficulty and frequent falls. Phisical examination revealed: mild scoliosis, elbow hyperextensibility, flat feet, chronic progressive external ophthalmoplegia with upper eyelid ptosis, diffuse hypotonia, and weakness of arm abduction and neck flexion. Investigation evidenced mild serum creatine kinase increase and glucose intolerance; second-degree atrioventricular block; mild mixed type respiratory disorder and atrophy and granular appearance of the retinal pigment epithelium. Brain magnetic resonance showed cerebellar atrophy. Muscle biopsy was compatible with mitochondrial myopathy. Genetic panel revealed a homozygous pathogenic variant in the MGME1 gene, consistent with MTDPS11 (c.862C > T; p.Gln288 *). This case of MTDPS11 can contribute to the phenotypic characterization of this ultra-rare mitochondrial disorder, presenting milder respiratory and nutritional involvement than the previously reported cases, with possible additional features.(c) 2023 Elsevier B.V. All rights reserved.
- SCA23 and prodynorphin: is it time for gene retraction?(2016) PEDROSO, Jose Luiz; VALE, Thiago Cardoso; FREUA, Fernando; BARSOTTINI, Orlando G. P.; KOK, Fernando
- NERVE CONDUCTION STUDIES IN SPASTIC PARAPLEGIA, OPTIC ATROPHY, AND NEUROPATHY (SPOAN) SYNDROME(2014) AMORIM, Simone; HEISE, Carlos Otto; SANTOS, Silvana; MACEDO-SOUZA, Lucia Ines; ZATZ, Mayana; KOK, FernandoIntroduction: SPOAN (spastic paraplegia, optic atrophy, and neuropathy) syndrome is an autosomal recessive neurodegenerative disorder identified in a large consanguineous Brazilian family. Methods: Twenty-seven patients with SPOAN syndrome (20 women), aged 4-58 years, underwent nerve conduction studies (NCS) of the median, ulnar, tibial, and fibular nerves, and sensory NCS of the median, ulnar, radial, sural, and superficial fibular nerves. Results: Sensory nerve action potentials were absent in the lower limbs and absent in >80% of upper limbs. Motor NCS had reduced amplitudes and borderline velocities in the upper limbs and absent compound muscle action potentials (CMAPs) in the lower limbs. Conclusions: The neuropathy in SPOAN syndrome is a severe, early-onset sensory-motor axonal polyneuropathy. Normal NCS seem to rule-out this condition. Muscle Nerve49: 131-133, 2014
- 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.
- Clinical Presentation of a Complex Neurodevelopmental Disorder Caused by Mutations in ADNP(2019) DIJCK, Anke Van; SILFHOUT, Anneke T. Vulto-van; CAPPUYNS, Elisa; WERF, Ilse M. van der; MANCINI, Grazia M.; TZSCHACH, Andreas; BERNIER, Raphael; GOZES, Illana; EICHLER, Evan E.; ROMANO, Corrado; LINDSTRAND, Anna; NORDGREN, Ann; KVARNUNG, Malin; KLEEFSTRA, Tjitske; VRIES, Bert B. A. de; KURY, Sebastien; ROSENFELD, Jill A.; MEUWISSEN, Marije E.; VANDEWEYER, Geert; KOOY, R. Frank; BAKSHI, Madhura; WILSON, Meredith; BERMAN, Yemina; DICKSON, Rebecca; FRANSEN, Erik; HELSMOORTEL, Celine; ENDE, Jenneke Van den; AA, Nathalie Van der; WIJDEVEN, Marina J. van de; ROSENBLUM, Jessica; MONTEIRO, Fabiola; KOK, Fernando; QUERCIA, Nada; BOWDIN, Sarah; DYMENT, David; CHITAYAT, David; ALKHUNAIZI, Ebba; BOONEN, Susanne E.; KEREN, Boris; JACQUETTE, Aurelia; FAIVRE, Laurence; BEZIEAU, Stephane; ISIDOR, Bertrand; RIESS, Angelika; MOOG, Ute; LYNCH, Sally Ann; MCVEIGH, Terri; ELPELEG, Orly; SMELAND, Marie Falkenberg; FANNEMEL, Madeleine; HAERINGEN, Arie van; MAAS, Saskia M.; VEENSTRA-KNOL, H. E.; SCHOUTEN, Meyke; WILLEMSEN, Marjolein H.; MARCELIS, Carlo L.; OCKELOEN, Charlotte; BURGT, Ineke van der; FEENSTRA, Ilse; SMAGT, Jasper van der; JEZELA-STANEK, Aleksandra; KRAJEWSKA-WALASEK, Malgorzata; GONZALEZ-LAMUNO, Domingo; ANDERLID, Britt-Marie; MALMGREN, Helena; NORDENSKJOLD, Magnus; CLEMENT, Emma; HURST, Jane; METCALFE, Kay; MANSOUR, Sahar; LACHLAN, Katherine; CLAYTON-SMITH, Jill; HENDON, Laura G.; ABDULRAHMAN, Omar A.; MORROW, Eric; MCMILLAN, Clare; GERDTS, Jennifer; PEEDEN, Joseph; VERGANO, Samantha A. Schrier; VALENTINO, Caitlin; CHUNG, Wendy K.; OZMORE, Jillian R.; BEDROSIAN-SERMONE, Sandra; DENNIS, Anna; TREAT, Kayla; HUGHES, Susan Starling; SAFINA, Nicole; PICHON, Jean-Baptiste Le; MCGUIRE, Marianne; INFANTE, Elena; MADAN-KHETARPAL, Suneeta; DESAI, Sonal; BENKE, Paul; KROKOSKY, Alyson; CRISTIAN, Ingrid; BAKER, Laura; GRIPP, Karen; STESSMAN, Holly A.; EICHENBERGER, Jacob; JAYAKAR, Parul; PIZZINO, Amy; MANNING, Melanie Ann; SLATTERY, LeahBACKGROUND: In genome-wide screening studies for de novo mutations underlying autism and intellectual disability, mutations in the ADNP gene are consistently reported among the most frequent. ADNP mutations have been identified in children with autism spectrum disorder comorbid with intellectual disability, distinctive facial features, and deficits in multiple organ systems. However, a comprehensive clinical description of the Helsmoortel-Van der Aa syndrome is lacking. METHODS: We identified a worldwide cohort of 78 individuals with likely disruptive mutations in ADNP from January 2014 to October 2016 through systematic literature search, by contacting collaborators, and through direct interaction with parents. Clinicians filled in a structured questionnaire on genetic and clinical findings to enable correlations between genotype and phenotype. Clinical photographs and specialist reports were gathered. Parents were interviewed to complement the written questionnaires. RESULTS: We report on the detailed clinical characterization of a large cohort of individuals with an ADNP mutation and demonstrate a distinctive combination of clinical features, including mild to severe intellectual disability, autism, severe speech and motor delay, and common facial characteristics. Brain abnormalities, behavioral problems, sleep disturbance, epilepsy, hypotonia, visual problems, congenital heart defects, gastrointestinal problems, short stature, and hormonal deficiencies are common comorbidities. Strikingly, individuals with the recurrent p.Tyr719* mutation were more severely affected. CONCLUSIONS: This overview defines the full clinical spectrum of individuals with ADNP mutations, a specific autism subtype. We show that individuals with mutations in ADNP have many overlapping clinical features that are distinctive from those of other autism and/or intellectual disability syndromes. In addition, our data show preliminary evidence of a correlation between genotype and phenotype.
- Aseptic meningitis in Fabry disease due to a novel GLA variant: an expanded phenotype?(2023) NOBREGA, Paulo Ribeiro; MORAIS, Joao Lucas Araujo; FERREIRA, Alliane Milliane; MEDEIROS, Alisson Dantas de; DUARTE, Beatrice Araujo; RANGEL, Deborah Moreira; LIMA, Fabricio Oliveira; PAIVA, Anderson Rodrigues Brandao de; PAIM-MARQUES, Luciana; KOK, Fernando; PESSOA, Andre Luiz Santos; BRAGA-NETO, Pedro; CARVALHO, Fernanda Martins MaiaBackground F abry disease (FD) is an X-linked lysosomal storage disorder with accumulation of globotriosylceramide, causing neurologic involvement mainly as acroparesthesias and cerebrovascular disease. Aseptic meningitis has been reported in 11 patients with FD, but no prior study has correlated alpha-galactosidase (GLA) specific variants with meningitis. We present in this manuscript a family in which a novel GLA pathogenic variant was associated with aseptic meningitis in 2 of 5 family members. Methods This study began with identifying the proband, then screening family members for FD symptoms and evaluating symptomatic individuals for genetic and biochemical status. All patients underwent magnetic resonance imaging, and those with headache underwent cerebrospinal fluid (CSF) analysis. Results Five patients (3 females) from a single family were included in this study. Mean age at diagnosis was 20.6 years. Two patients (40%) had aseptic meningitis; one of them also had cerebrovascular events. C-reactive protein and erythrocyte sedimentation rate were elevated during aseptic meningitis episodes. Both patients responded to intravenous methylprednisolone with resolution of fever, headache, and vomiting. One of them recurred and needed chronic immunosuppression with azathioprine. Conclusion We described aseptic meningitis in a family with a novel GLA variant. Meningitis might be a common phenomenon in FD and not a particularity of this variant. Understanding the mechanisms underlying meningitis and its association with cerebrovascular events may lead to a new paradigm of treatment for stroke in these patients. Further prospective studies with CSF collection in patients with FD and recurrent headache could help to elucidate this question.
- Subacute Partially Reversible Leukoencephalopathy Expands the Aicardi-Goutieres Syndrome Phenotype(2023) BARCELOS, Isabella Peixoto de; BUENO, Clarissa; GODOY, Luis Filipe S.; PESSOA, Andre; COSTA, Larissa A.; MONTI, Fernanda C.; SOUZA-CABRAL, Katiane; LISTIK, Clarice; CASTRO, Diego; DELLA-RIPA, Bruno; FREUA, Fernando; PIRES, Lais C.; KRUGER, Lia T.; GHERPELLI, Jose Luiz D.; PIAZZON, Flavia B.; MONTEIRO, Fabiola P.; LUCATO, Leandro T.; KOK, FernandoObjective: To report a series of atypical presentations of Aicardi-Goutieres syndrome. Methods: Clinical, neuroimaging, and genetic data. Results: We report a series of six unrelated patients (five males) with a subacute loss of developmental milestones, pyramidal signs, and regression of communication abilities, with onset at ages ranging from 7 to 20 months, reaching a nadir after 4 to 24 weeks. A remarkable improvement of lost abilities occurred in the follow-up, and they remained with residual spasticity and dysarthria but preserved cognitive function. Immunization or febrile illness occurred before disease onset in all patients. CSF was normal in two patients, and in four, borderline or mild lymphocytosis was present. A brain CT scan disclosed a subtle basal ganglia calcification in one of six patients. Brain MRI showed asymmetric signal abnormalities of white matter with centrum semi-ovale involvement in five patients and a diffuse white matter abnormality with contrast enhancement in one. Four patients were diagnosed and treated for acute demyelinating encephalomyelitis (ADEM). Brain imaging was markedly improved with one year or more of follow-up (average of 7 years), but patients remained with residual spasticity and dysarthria without cognitive impairment. Demyelination relapse occurred in a single patient four years after the first event. Whole-exome sequencing (WES) was performed in all patients: four of them disclosed biallelic pathogenic variants in RNASEH2B (three homozygous p.Ala177Thr and one compound heterozygous p.Ala177Thr/p.Gln58*) and in two of them the same homozygous deleterious variants in RNASEH2A (p.Ala249Val). Conclusions: This report expands the phenotype of AGS to include subacute developmental regression with partial clinical and neuroimaging improvement. Those clinical features might be misdiagnosed as ADEM.
conferenceObject Childhood Amyotrophic Lateral Sclerosis Caused by Excess Sphingolipid Synthesis(2021) MOHASSEL, Payam; DONKERVOORT, Sandra; LONE, Museer A.; NALLS, Matthew A.; GABLE, Kenneth; GUPTA, Sita D.; FOLEY, A. Reghan; HU, Ying; SAUTE, Jonas Alex Morales; MOREIRA, Ana Lucila; KOK, Fernando; INTRONA, Alessandro; LOGROSCINO, Giancarlo; GRUNSEICH, Christopher; NICKOLLS, Alec; POURSHAFIE, Naemeh; NEUHAUS, Sarah B.; SAADE, Dimah; GANGFUSS, Andrea; KOELBEL, Heike; PICCUS, Zoe; PICHON, Claire E. Le; FIORILLO, Chiara; LY, Cindy V.; TOPF, Ana; BRADY, Lauren; SPECHT, Sabine; ZIDELL, Aliza; PEDRO, Helio; MITTELMANN, Eric; THOMAS, Florian P.; CHAO, Katherine R.; KONERSMAN, Chamindra G.; CHO, Megan T.; BRANDT, Tracy; STRAUB, Volker; CONNOLLY, Anne M.; SCHARA, Ulrike; ROOS, Andreas; TARNOPOLSKY, Mark; HOKE, Ahmet; BROWN JR., Robert H.; LEE, Chia-Hsueh; HORNEMANN, Thorsten; DUNN, Teresa M.; BOENNEMANN, Carsten G.