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
15 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 15
- 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
- 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.
- 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.
- Typical clinical and neuroimaging features in Sjogren-Larsson syndrome(2018) PAIVA, Anderson Rodrigues Brandao de; MELO, Uira Souto; FREUA, Fernando; DORIA, Denise; CABRAL, Katiane Sayao Souza; MACEDO-SOUZA, Lucia Ines; LUCATO, Leandro Tavares; KOK, Fernando
- A homozygous loss-of-function mutation in inositol monophosphatase 1 (IMPA1) causes severe intellectual disability(2016) FIGUEIREDO, T.; MELO, U. S.; PESSOA, A. L. S.; NOBREGA, P. R.; KITAJIMA, J. P.; RUSCH, H.; VAZ, F.; LUCATO, L. T.; ZATZ, M.; KOK, F.; SANTOS, S.The genetic basis of intellectual disability (ID) is extremely heterogeneous and relatively little is known about the role of autosomal recessive traits. In a field study performed in a highly inbred area of Northeastern Brazil, we identified and investigated a large consanguineous family with nine adult members affected by severe ID associated with disruptive behavior. The Genome-Wide Human SNP Array 6.0 microarray was used to determine regions of homozygosity by descent from three affected and one normal family member. Whole-exome sequencing (WES) was performed in one affected patient using the Nextera Rapid-Capture Exome kit and Illumina HiSeq2500 system to identify the causative mutation. Potentially deleterious variants detected in regions of homozygosity by descent and not present in either 59 723 unrelated individuals from the Exome Aggregation Consortium (Browser) or 1484 Brazilians were subject to further scrutiny and segregation analysis by Sanger sequencing. Homozygosity-by-descent analysis disclosed a 20.7-Mb candidate region at 8q12.3-q21.2 (lod score: 3.11). WES identified a homozygous deleterious variant in inositol monophosphatase 1 (IMPA1) (NM_005536), consisting of a 5-bp duplication (c.489_493dupGGGCT; chr8: 82,583,247; GRCh37/hg19) leading to a frameshift and a premature stop codon (p.Ser165Trpfs*10) that cosegregated with the disease in 26 genotyped family members. The IMPA1 gene product is responsible for the final step of biotransformation of inositol triphosphate and diacylglycerol, two second messengers. Despite its many physiological functions, no clinical phenotype has been assigned to this gene dysfunction to date. Additionally, IMPA1 is the main target of lithium, a drug that is at the forefront of treatment for bipolar disorder.
- Chronic stage of Marchiafava-Bignami disease(2015) LUCATO, Leandro Tavares; FREUA, Fernando; KOK, Fernando
- Leukodystrophy with premature ovarian failure: think on vanishing white matter disease (VWMD)(2015) FREUA, Fernando; PARMERA, Jacy Bezerra; DORIA, Denise de Oliveira; PAIVA, Anderson Rodrigues Brandao de; MACEDO-SOUZA, Lucia Ines; KOK, Fernando
article - Clinical management and diagnosis of CLN2 disease: consensus of the Brazilian experts group(2023) SAMPAIO, Leticia Pereira de Brito; MANREZA, Maria Luiza Giraldes de; PESSOA, Andre; GURGEL-GIANNETTI, Juliana; COAN, Ana Carolina; LINDEN JUNIOR, Helio van der; EMBIRUCU, Emilia Katiane; HENRIQUES-SOUZA, Adelia Maria de Miranda; KOK, FernandoNeuronal ceroid lipofuscinosis type 2 (CLN2) is a rare neurodegenerative genetic disease that affects children in early life. Its classic form is rapidly progressive, leading to death within the first 10 years. The urge for earlier diagnosis increases with the availability of enzyme replacement therapy. A panel of nine Brazilian child neurologists combined their expertise in CLN2 with evidence from the medical literature to establish a consensus to manage this disease in Brazil. They voted 92 questions including diagnosis, clinical manifestations, and treatment of the disease, considering the access to healthcare in this country. Clinicians should suspect CLN2 disease in any child, from 2 to 4 years old, with language delay and epilepsy. Even though the classic form is the most prevalent, atypical cases with different phenotypes can be found. Electroencephalogram, magnetic resonance imaging, molecular and biochemical testing are the main tools to investigate and confirm the diagnosis. However, we have limited access to molecular testing in Brazil, and rely on the support from the pharmaceutical industry. The management of CLN2 should involve a multidisciplinary team and focus on the quality of life of patients and on family support. Enzyme replacement therapy with Cerliponase a is an innovative treatment approved in Brazil since 2018; it delays functional decline and provides quality of life. Given the difficulties for the diagnosis and treatment of rare diseases in our public health system, the early diagnosis of CLN2 needs improvement as enzyme replacement therapy is available and modifies the prognosis of patients.
- Imaging of adult leukodystrophies(2014) LEITE, Claudia Costa; LUCATO, Leandro Tavares; SANTOS, Germano Titoneli; KOK, Fernando; BRANDAO, Anderson Rodrigues; CASTILLO, MauricioLeukodystrophies are genetically determined white matter disorders. Even though leukodystrophies essentially affect children in early infancy and childhood, these disorders may affect adults. In adults, leukodystrophies may present a distinct clinical and imaging presentation other than those found in childhood. Clinical awareness of late-onset leukodystrophies should be increased as new therapies emerge. MRI is a useful tool to evaluate white matter disorders and some characteristics findings can help the diagnosis of leukodystrophies. This review article briefly describes the imaging characteristics of the most common adult leukodystrophies.