Familial Creutzfeldt-Jakob disease associated with a point mutation at codon 210 of the prion protein gene

Abstract

-Creutzfeldt-Jakob disease (CJD), the most known human prion disease, is usually sporadic but approximately 15% of the cases are familial. To date, seven CJD cases with codon 210 mutation (GTT to ATT) have been reported in the literature. We describe a case of a 57 year-old woman who presented gait disturbances and rapidly progressive dementia, leading to death four months after onset. Electroencephalogram revealed periodic activity, diffusion-weighted magnetic resonance imaging showed hypersignal in basal ganglia, and test for 14-3-3 protein was strongly positive in the CSF. The complete prion protein gene coding region was sequenced after PCR amplification, showing a point mutation in codon 210. This is the first case of CJD with codon 210 mutation diagnosed in Brazil. We emphasize the role of genetic search for prion protein gene mutation, even in patients presenting clinical features resembling sporadic CJD.KEY WORDS: familial Creutzfeldt-Jakob disease, prion protein gene mutation, codon 210, 14-3-3 protein. Doença de Creutzfeldt-Jakob familial com mutação pontual no codon 210 do gene da proteína priônicaRESUMO -A doença de Creutzfeldt-Jakob (DCJ), a mais conhecida das doenças priônicas, é usualmente esporádica, mas cerca de 15% dos casos são familiais. Sete casos de DCJ familial com mutação no codon 210 (GTT→ATT) foram relatados na literatura até o presente momento. Nós descrevemos o caso de uma mulher de 57 anos com distúrbios de marcha e demência rapidamente progressiva, evoluindo para óbito em 4 meses. Eletroencefalograma revelou atividade periódica, ressonância magnética com técnica de difusão mostrou hipersinal em gânglios da base e teste para proteína 14-3-3 no líquido cefalorraqueano foi fortemente positivo. A região codificadora do gene da proteína priônica foi sequenciada após a amplificação por PCR, revelando mutação de ponto no codon 210, constituindo-se no primeiro caso com esta mutação diagnosticado no Brasil. Enfatizamos a importância da investigação de mutações do gene da proteína priônica, mesmo em pacientes com quadro típico de DCJ esporádica. PALAVRAS-CHAVE: doença de Creutzfeldt-Jakob familial, codon 210, gene da proteína priônica, mutação, proteína 14-3-3.

Diffusion-weighted MRI in familial Creutzfeldt–Jakob disease with the codon 200 mutation in the prion protein gene

“…For example, MRI with diffusion-weighted images (DWI) shows increased signals in the basal ganglia and cerebral cortex of patients with sporadic CJD [19][20][21][22][23][24][25][26][27][28]. Whether MRI is equally useful in the diagnosis of familial CJD remains unclear, although several MRI studies have been reported in familial CJD with various mutations in the prion protein gene [29][30][31][32].…”

Creutzfeldt-Jakob disease associated with a missense mutation at codon 200 of the prion protein gene in Brazil

“…To date, two cases of acquired CJD associated with human growth hormone therapy have been reported, 14 , 15 while only two genetic forms of CJD associated with mutation at codon 210 and at codon 183 have been described. 16 , 17 The clinical presentation of fCJD associated with E200K is quite similar to sCDJ. Studies have shown similar mean age of onset, mean duration of disease, as well as similar presenting symptoms and clinical courses.…”

PSEN1 and PRNP Gene Mutations Co-occurrence Makes Onset Very Early in a Family with FTD Phenotype

“…A molecular screening of PRNP and PSEN1 genes was performed by bidirectional sequencing analysis on an ABI310 automated sequencer (Applied Biosystems) using the Big Dye kit (Perkin Elmer) and previously reported specific PCR primers [15,16]. The APOE genotype, H1/H2 MAPT gene haplotype and Prion protein (PRNP) Met129Val polymorphism were assessed as described previously [17][18][19].…”