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
11 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 11
- 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.
- Clinical aspects of hereditary spastic paraplegia 76 and novel CAPN1 mutations(2018) MELO, U. S.; FREUA, F.; LYNCH, D. S.; RIPA, B. D.; TENORIO, R. B.; SAUTE, J. A. M.; LEITE, F. de Souza; KITAJIMA, J.; HOULDEN, H.; ZATZ, M.; KOK, F.
- Parental germline mosaicism in SCN3A-related severe developmental disorder(2021) INUZUKA, Luciana Midori; MACEDO-SOUZA, Lucia Ines; GUERRA-PEIXE, Matheus; PEDREIRA, Christiane Cobas; DELLA-RIPA, Bruno; DELGADO, Daniel Souza; MONTEIRO, Fabiola; KITAJIMA, Joao Paulo; GARZON, Eliana; KOK, Fernando
- Neurodevelopmental disorder associated with de novo SCN3A pathogenic variants: Two new cases and review of the literature (vol 42, pg 211, 2020)(2021) 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, Eliana
- Brain or Spinal Cord MRI in the Investigation of Hereditary Spastic Paraplegia? Brain First!(2020) FREUA, F.; RIPA, B. D.; IMACEDO-SOUZA, L.; PAIVA, A. R. B.; KOK, F.
- Additional observation of a de novo pathogenic variant in KCNT2 leading to epileptic encephalopathy with clinical features of frontal lobe epilepsy(2020) INUZUKA, Luciana Midori; MACEDO-SOUZA, Lucia Ines; DELLA-RIPA, Bruno; MONTEIRO, Fabiola Paoli; RAMOS, Luiza; KITAJIMA, Joao Paulo; GARZON, Eliana; KOK, FernandoIntroduction: KCNT2 was recently recognized as a gene associated with neurodevelopmental disorder and epilepsy. Case report: We present an additional observation of a 16-year-old male patient with a novel de novo KCNT2 likely pathogenic variant and review the five previously reported cases of de novo variants in this gene. Discussion: Whole exome sequencing identified the missense variant c.725C > A p.(Thr242Asn), which was confirmed by Sanger sequencing. Our patient has a refractory stereotyped and monomorphic type of hyperkinetic focal motor seizure, similar to what is seen in frontal lobe epilepsy, occurring only during sleep. This type of seizure is not usually seen in epileptic encephalopathies.
- A novel complex neurological phenotype due to a homozygous mutation in FDX2(2018) GURGEL-GIANNETTI, Juliana; LYNCH, David S.; PAIVA, Anderson Rodrigues Brandao de; LUCATO, Leandro Tavares; YAMAMOTO, Guilherme; THOMSEN, Christer; BASU, Somsuvro; FREUA, Fernando; GIANNETTI, Alexandre Varella; ASSIS, Bruno Della Ripa de; RIBEIRO, Mara Dell Ospedale; BARCELOS, Isabella; SOUZA, Katiane Sayao; MONTI, Fernanda; MELO, Uira Souto; AMORIM, Simone; SILVA, Leonardo G. L.; MACEDO-SOUZA, Lucia Ines; VIANNA-MORGANTE, Angela M.; HIRANO, Michio; KNAAP, Marjo S. Van der; LILL, Roland; VAINZOF, Mariz; OLDFORS, Anders; HOULDEN, Henry; KOK, FernandoDefects in iron-sulphur [Fe-S] cluster biogenesis are increasingly recognized as causing neurological disease. Mutations in a number of genes that encode proteins involved in mitochondrial [Fe-S] protein assembly lead to complex neurological phenotypes. One class of proteins essential in the early cluster assembly are ferredoxins. FDX2 is ubiquitously expressed and is essential in the de novo formation of [2Fe-2S] clusters in humans. We describe and genetically define a novel complex neurological syndrome identified in two Brazilian families, with a novel homozygous mutation in FDX2. Patients were clinically evaluated, underwent MRI, nerve conduction studies, EMG and muscle biopsy. To define the genetic aetiology, a combination of homozygosity mapping and whole exome sequencing was performed. We identified six patients from two apparently unrelated families with autosomal recessive inheritance of a complex neurological phenotype involving optic atrophy and nystagmus developing by age 3, followed by myopathy and recurrent episodes of cramps, myalgia and muscle weakness in the first or second decade of life. Sensory-motor axonal neuropathy led to progressive distal weakness. MRI disclosed a reversible or partially reversible leukoencephalopathy. Muscle biopsy demonstrated an unusual pattern of regional succinate dehydrogenase and cytochrome c oxidase deficiency with iron accumulation. The phenotype was mapped in both families to the same homozygous missense mutation in FDX2 (c. 431C > T, p. P144L). The deleterious effect of the mutation was validated by real-time reverse transcription polymerase chain reaction and western blot analysis, which demonstrated normal expression of FDX2 mRNA but severely reduced expression of FDX2 protein in muscle tissue. This study describes a novel complex neurological phenotype with unusual MRI and muscle biopsy features, conclusively mapped to a mutation in FDX2, which encodes a ubiquitously expressed mitochondrial ferredoxin essential for early [Fe-S] cluster biogenesis.
- ATP6V1B2-related epileptic encephalopathy(2020) INUZUKA, Luciana Midori; MACEDO-SOUZA, Lucia Ines; DELLA-RIPPA, Bruno; MONTEIRO, Fabiola Paoli; DELGADO, Daniel de Souza; GODOY, Luis Filipe; RAMOS, Luiza; COSTA, Larissa Sampaio de Athayde; GARZON, Eliana; KOK, FernandoATP6V1B2 encodes a subunit of the lysosomal transmembrane proton pump necessary for adequate functioning of several acidhydrolases. De novo monoallelic variants of this gene have been associated with two distinct phenotypes: Zimmermann-Laband syndrome 2 (ZLS2), an intellectual deficiency/multiple malformation syndrome, and dominant deafness onychodystrophy(DDOD), a multiple malformation syndrome without cognitive involvement. Epilepsy is not observed in DDOD, is variably present in ZLS2, but is a common feature in Zimmermann-Laband syndrome 1 (ZLS1) (caused by monoallelic pathogenic variants in KCNH1) and Zimmermann-Laband syndrome-like (ZLSL) (associated with KCNK4 variants). Herein, we report a case of an infant with severe epileptic encephalopathy with microcephaly and profound developmental delay, associated with a novel de novo loss-of-function variant in ATP6V1B2, diagnosed by whole-exome sequencing. This finding expands the spectrum of ATP6V1B2-associated disorders and adds ATP6V1B2 as a new member for the growing list of early-onset epileptic encephalopathy genes.
bookPart Ataxias de origem genética(2021) ASSIS, Bruno Della Ripa Rodrigues; KOK, Fernando- 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.