Análise da presença de mutação no gene TARDBP em pacientes com degeneração lobar frontotemporal e implementação de metodologia para determinação dos polimorfismos do gene APOE em pacientes com Doença de Alzheimer em São Paulo - SP

Costa, Thaís Virgínia Moura Machado

doi:10.11606/d.5.2012.tde-02102012-084400

Cited by 3 publications

(4 citation statements)

References 41 publications

(56 reference statements)

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“…24 TARDBP is a gene in chromosome 1 that encodes a protein called TDP-43, an important riboprotein with functions such as mRNA stabilization, transcription regulation, and alternative splicing. 6,25 Mutations in this gene have been associated with FTD, FTD-ALS, and ALS. 25 In 2012, Machado-Costa screened a sample of 47 FTD cases for TARDBP mutations and found a p.I383V mutation in a proband diagnosed with svPPA at the age of 54.…”

Section: Grn Mapt and Tardbp Mutationsmentioning

confidence: 99%

“…6,25 Mutations in this gene have been associated with FTD, FTD-ALS, and ALS. 25 In 2012, Machado-Costa screened a sample of 47 FTD cases for TARDBP mutations and found a p.I383V mutation in a proband diagnosed with svPPA at the age of 54. 25 The mutation carrier also had neuropsychiatric symptoms like irritability, apathy, disinhibition, and obsessive-compulsive behavior; his brain MRI showed bilateral temporal atrophy.…”

Section: Grn Mapt and Tardbp Mutationsmentioning

confidence: 99%

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Genetics of dementia: insights from Latin America

Ramos

Aguillón

Cordano³

et al. 2020

Dement. neuropsychol.

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ABSTRACT. Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are neurodegenerative disorders that result in a significant burden to both patients and caregivers. By 2050, the number of people with dementia in Latin America will increase 4-fold. A deep understanding of the relevant genetic factors of AD and FTD is fundamental to tackle this reality through prevention. A review of different genetic variants that cause AD or FTD in Latin America was conducted. We searched Medline and PubMed databases using the keywords “Alzheimer’s disease,” “frontotemporal dementia,” “mutation,” “America,” and “Latin America,” besides specific Latin American countries. Forty-five items were chosen and analyzed. PSEN1 mutations are the commonest cause of genetic early-onset Alzheimer’s disease (EOAD), followed by PSEN2 and APP mutations. Genetic FTD can be mainly explained by GRN and MAPT mutations, as well as C9orf72 G4C2 repeat expansion. APOE ε4 can modify the prevalence and incidence of late-onset Alzheimer’s disease (LOAD), in addition to the cognitive performance in affected carriers.

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Section: Grn Mapt and Tardbp Mutationsmentioning

confidence: 99%

Section: Grn Mapt and Tardbp Mutationsmentioning

confidence: 99%

Genetics of dementia: insights from Latin America

Ramos

Aguillón

Cordano³

et al. 2020

Dement. neuropsychol.

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“…In Brazil, Machado-Costa identified a TARDBP mutation in a 54-year-old patient diagnosed with semantic dementia. This mutation was identified in the exon 6 of TARDBP corresponding to a p.I1383V mutation ( 88 ).…”

Section: Resultsmentioning

confidence: 99%

Systematic Review: Genetic, Neuroimaging, and Fluids Biomarkers for Frontotemporal Dementia Across Latin America Countries

et al. 2021

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Frontotemporal dementia (FTD) includes a group of clinically, genetically, and pathologically heterogeneous neurodegenerative disorders, affecting the fronto-insular-temporal regions of the brain. Clinically, FTD is characterized by progressive deficits in behavior, executive function, and language and its diagnosis relies mainly on the clinical expertise of the physician/consensus group and the use of neuropsychological tests and/or structural/functional neuroimaging, depending on local availability. The modest correlation between clinical findings and FTD neuropathology makes the diagnosis difficult using clinical criteria and often leads to underdiagnosis or misdiagnosis, primarily due to lack of recognition or awareness of FTD as a disease and symptom overlap with psychiatric disorders. Despite advances in understanding the underlying neuropathology of FTD, accurate and sensitive diagnosis for this disease is still lacking. One of the major challenges is to improve diagnosis in FTD patients as early as possible. In this context, biomarkers have emerged as useful methods to provide and/or complement clinical diagnosis for this complex syndrome, although more evidence is needed to incorporate most of them into clinical practice. However, most biomarker studies have been performed using North American or European populations, with little representation of the Latin American and the Caribbean (LAC) region. In the LAC region, there are additional challenges, particularly the lack of awareness and knowledge about FTD, even in specialists. Also, LAC genetic heritage and cultures are complex, and both likely influence clinical presentations and may modify baseline biomarker levels. Even more, due to diagnostic delay, the clinical presentation might be further complicated by both neurological and psychiatric comorbidity, such as vascular brain damage, substance abuse, mood disorders, among others. This systematic review provides a brief update and an overview of the current knowledge on genetic, neuroimaging, and fluid biomarkers for FTD in LAC countries. Our review highlights the need for extensive research on biomarkers in FTD in LAC to contribute to a more comprehensive understanding of the disease and its associated biomarkers. Dementia research is certainly reduced in the LAC region, highlighting an urgent need for harmonized, innovative, and cross-regional studies with a global perspective across multiple areas of dementia knowledge.

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“…Dentre os 15 probandos com antecedente familiar de DFT, em apenas seis (40%) a mutação causadora foi identificada em MAPT ou GRN. Em um outro probando (DFT 46), diagnosticado com vsAPP, foi previamente identificada uma mutação p.I383V no gene TARDBP 244.…”

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Pesquisa de mutações do gene GRN e dosagem plasmática de progranulina em casuística brasileira de degeneração lobar frontotemporal

Takada¹

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Introdução: A demência frontotemporal (DFT) inclui a variante comportamental da demência frontotemporal (vcDFT), a variante semântica da afasia progressiva primária (vsAPP), e a variante não fluente da APP (vnfAPP). Os genes em que são encontradas mutações causadoras de DFT mais frequentemente são: GRN (que codifica a progranulina), MAPT (que codifica a proteína tau) e C9orf72. Métodos: Foram incluídos probandos diagnosticados com vcDFT, vsAPP ou vnfAPP, com base com os critérios diagnósticos mais recentes, e um grupo de indivíduos cognitivamente normais. Os éxons 2-12 de GRN e os éxons 1, 9-13 de MAPT foram sequenciados pelo método de Sanger, e foi realizada dosagem de progranulina no plasma. Resultados: foram incluídos 62 probandos, sendo 44 com vcDFT, 9 com vsAPP, e 9 com vnfAPP. Antecedente familiar de demência foi positivo em 45,1% dos probandos, e de DFT, em 24,1%. Os 60 indivíduos do grupo controle tinham idade média de 60,8±8,5 anos. Foram identificadas seis mutações nulas em GRN (p.Q130X, p.V200Gfs*18, p.Q257Pfs*26, p.Q300X, p.S301Cfs*60 e p.D317Afs*11) e uma mutação patogênica em MAPT (p.N279K). A dosagem média de progranulina plasmática nos pacientes com mutações de GRN foi de 29,8±11,9ng/ml Conclusões: A frequência de mutações patogênicas em GRN nesta casuística foi de 9,6%, e a de mutações em MAPT foi de 1,6%. Entre casos familiais de DFT, a frequência de mutações em GRN foi de 33,3%, e em MAPT foi de 6,7%. Duas das mutações encontradas em GRN (p.Q130X e p.D317Afs*11) ainda não foram descritas em casos de DFT. O valor de corte de 70ng/ml identificou as mutações nulas de GRN com sensibilidade e especificidade de 100%. Descritores: degeneração lobar frontotemporal; demência frontotemporal; afasia primária progressiva não fluente; genética; tauopatias; proteinopatias TDP-43; mutação.

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Análise da presença de mutação no gene TARDBP em pacientes com degeneração lobar frontotemporal e implementação de metodologia para determinação dos polimorfismos do gene APOE em pacientes com Doença de Alzheimer em São Paulo - SP

Cited by 3 publications

References 41 publications

Genetics of dementia: insights from Latin America

Genetics of dementia: insights from Latin America

Systematic Review: Genetic, Neuroimaging, and Fluids Biomarkers for Frontotemporal Dementia Across Latin America Countries

Pesquisa de mutações do gene GRN e dosagem plasmática de progranulina em casuística brasileira de degeneração lobar frontotemporal

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