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
118 resultados
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- Neurodevelopmental disorder associated with de novo SCN3A pathogenic variants: two new cases and review of the literature(2020) INUZUKA, Luciana Midori; MACEDO-SOUZA, Lucia Ines; DELLA-RIPA, Bruno; CABRAL, Katiane S. S.; MONTEIRO, Fabiola; KITAJIMA, Joao Paulo; GODOY, Luis Filipe de Souza; DELGADO, Daniel de Souza; KOK, Fernando; GARZON, ElianaSCN3A was recently recognized as a gene associated with neurodevelopmental disorder and epilepsy. We present two additional patients with a novel de novo SCN3A pathogenic variant, and a review of all published cases of de novo variants. In one of our patients brain magnetic resonance imaging (MRI) disclosed a severe polymicrogyria and in the other it was normal. The clinical phenotype was characterized by a severe developmental delay and refractory epilepsy in the patient with polymicrogyria and intellectual disability with autistic features and pharmacoresponsive epilepsy in the subject with normal MRI. Polymicrogyria, a disorder of progenitor cells proliferation and migration, is an unanticipated finding for an ion channel dysfunction.
- Homozygous missense mutation in MED25 segregates with syndromic intellectual disability in a large consanguineous family(2015) FIGUEIREDO, Thalita; MELO, Uira Souto; PESSOA, Andre Luiz Santos; NOBREGA, Paulo Ribeiro; KITAJIMA, Joao Paulo; CORREA, Igor; ZATZ, Mayana; KOK, Fernando; SANTOS, SilvanaBackground Intellectual disability (ID) is a highly heterogeneous condition affecting 2% of the population worldwide. In a field study conducted in a highly inbred area of Northeastern Brazil, we investigated a consanguineous family in which seven adults presented syndromic ID. Methods Genome-Wide Human SNP Array 6.0 (Affymetrix) microarray was used to determine regions of homozygosity-by-descent and whole exome sequencing (WES) was performed in one affected individual using Extended Nextera Rapid-Capture Exome and Illumina HiSeq2500. Results We found two regions with an logarithm of the odds (LOD) score of 3.234: a region spanning 4.0 Mb in 19q13.32-q13.33 and a pericentromeric 20 Mb area in chromosome 2 (2p12-q11.2). WES disclosed in the critical region of chromosome 19 a homozygous variant (c.418C> T, p.Arg140Trp) in Mediator complex subunit 25 (MED25), predicted as deleterious by PolyPhen-2, Provean, Mutation Taster and Sorting Intolerant From Tolerant (SIFT). MED25 is a component of the Mediator complex, involved in regulation of transcription of nearly all RNA polymerase II-dependent genes. Deleterious mutations in MED12, MED17 and MED23 have already been associated with ID. Conclusions These findings demonstrate that the combination of field investigation of families in highly inbred regions with modern technologies is an effective way for identifying new genes associated with ID.
- Quadrupedal gait and cerebellar hypoplasia, the Uner Tan syndrome, caused by ITPR1 gene mutation(2021) RASLAN, Ivana Rocha; FRANCA, Marcondes Cavalcante; OLIVEIRA, Joao Bosco; SCHUURS-HOEIJMAKERS, Janneke H. M.; PFUNDT, Rolph; KOK, Fernando; BARSOTTINI, Orlando Graziani Povoas; PEDROSO, Jose Luiz
- 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.
- Ceroid lipofuscinosis type 5: novel pathogenic variants and unexpected phenotypic findings(2023) PAIVA, Anderson Rodrigues Brandao de; PESSOA, Andre Luiz Santos; NOBREGA, Paulo Ribeiro; MORENO, Cristiane Araujo Martins; LYNCH, David S.; TANIGUTI, Lucas Mitsuo; KITAJIMA, Joao Paulo; FREUA, Fernando; DELLA-RIPA, Bruno; CUNHA, Paulina; BARCELOS, Isabella Peixoto de; MACEDO-SOUZA, Lucia Ines; TAKEUCHI, Carlos Augusto; GARCIA, Antonio Milton Silva; NARDES, Flavia; FONTAO, Ramiro; ANTONIUK, Sergio Antonio; TRONCOSO, Monica; SPECOLA, Norma; DURAND, Consuelo; MADEIRO, Bianca de Aguiar Coelho Silva; DORIQUI, Maria Juliana Rodovalho; VERGARA, Diane; HOULDEN, Henry; KOK, Fernando
- GNBS Mutations Cause an Autosomal-Recessive Multisystem Syndrome with Sinus Bradycardia and Cognitive Disability(2016) LODDER, Elisabeth M.; NITTIS, Pasquelena De; KOOPMAN, Charlotte D.; WISZNIEWSKI, Wojciech; SOUZA, Carolina Fischinger Moura de; LAHROUCHI, Najim; GUEX, Nicolas; NAPOLIONI, Valerio; TESSADORI, Federico; BEEKMAN, Leander; NANNENBERG, Eline A.; BOUALLA, Lamiae; BLOM, Nico A.; GRAAFF, Wim de; KAMERMANS, Maarten; COCCIADIFERRO, Dario; MALERBA, Natascia; MANDRIANI, Barbara; AKDEMIR, Zeynep Hande Coban; FISH, Richard J.; ELDOMERY, Mohammad K.; RATBI, Ilham; WILDE, Arthur A. M.; BOER, Teun de; SIMONDS, William F.; NEERMAN-ARBEZ, Marguerite; SUTTON, V. Reid; KOK, Fernando; LUPSKI, James R.; REYMOND, Alexandre; BEZZINA, Connie R.; BAKKERS, Jeroen; MERLA, GiuseppeGNB5 encodes the G protein beta subunit 5 and is involved in inhibitory G protein signaling. Here, we report mutations in GNB5 that are associated with heart-rate disturbance, eye disease, intellectual disability, gastric problems, hypotonia, and seizures in nine individuals from six families. We observed an association between the nature of the variants and clinical severity; individuals with loss-of-function alleles had more severe symptoms, including substantial developmental delay, speech defects, severe hypotonia, pathological gastro-esophageal re flux, retinal disease, and sinus-node dysfunction, whereas related heterozygotes harboring missense variants presented with a clinically milder phenotype. Zebrafish gnb5 knockouts recapitulated the phenotypic spectrum of affected individuals, including cardiac, neurological, and ophthalmological abnormalities, supporting a direct role of GNB5 in the control of heart rate, hypotonia, and vision.
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.- Quantification of functional abilities in Rett syndrome: a comparison between stages III and IV(2014) MONTEIRO, Carlos B. M.; SAVELSBERGH, Geert J. P.; SMORENBURG, Ana R. P.; GRACIANI, Zodja; TORRIANI-PASIN, Camila; ABREU, Luiz Carlos de; VALENTI, Vitor E.; KOK, FernandoWe aimed to evaluate the functional abilities of persons with Rett syndrome (RTT) in stages III and IV. The group consisted of 60 females who had been diagnosed with RTT: 38 in stage III, mean age (years) of 9.14, with a standard deviation of 5.84 (minimum 2.2/maximum 26.4); and 22 in stage IV, mean age of 12.45, with a standard deviation of 6.17 (minimum 5.3/maximum 26.9). The evaluation was made using the Pediatric Evaluation of Disability Inventory, which has 197 items in the areas of self-care, mobility, and social function. The results showed that in the area of self-care, stage III and stage IV RTT persons had a level of 24.12 and 18.36 (P=0.002), respectively. In the area of mobility, stage III had 37.22 and stage IV had 14.64 (P<0.001), while in the area of social function, stage III had 17.72 and stage IV had 12.14 (P=0.016). In conclusion, although persons with stage III RTT have better functional abilities when compared with stage IV, the areas of mobility, self-care, and social function are quite affected, which shows a great functional dependency and need for help in basic activities of daily life.
- A endogamia explicaria a elevada prevalência de deficiências em populações do Nordeste brasileiro?(2013) SANTOS, Silvana Cristina dos; MELO, Uira Souto; LOPES, Simone Silva dos Santos; WELLER, Mathias; KOK, FernandoDespite conceptual inaccuracies and methods of measurement, the WHO estimates that about 10% of the world population has some form of disability. In order to investigate the prevalence and etiology of disabilities and to evaluate if they could be associated with inbreeding, a cross-sectional epidemiological study was conducted using the informant method in five communities of the state Rio Grande do Norte in the Brazilian Northeast, in which consanguineous marriages frequencies varied between 9 and 32%. The average prevalence of disabilities in the five sampled communities was 4.53%, obtained by interviews that involved 37.87% of a population of 39,054 inhabitants. On average, 25% of consanguineous and 12% of non-consanguineous couples had one or more children with disabilities. The increased rate of individuals with disabilities in the Brazilian Northeast could be associated with the maintenance of the tradition of consanguineous marriages in these populations and some of these disabilities may be caused by genetic disorders.
bookPart Lucodistrofias no adulto(2021) PAIVA, Anderson Rodrigues Brandão; KOK, Fernando