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Query: UMLS:C0004134 (
ataxia
)
15,886
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Prion diseases are neurodegenerative disorders which are caused by an accumulation of the abnormal, misfolded prion protein known as
scrapie prion protein
(PrP
Sc
). These disorders are unique as they occur as sporadic, genetic and acquired forms. Sporadic Creutzfeldt-Jakob Disease (CJD) is the most common human prion disease, accounting for approximately 85-90% of cases, whereas autosomal dominant genetic forms, due to mutations in the prion protein gene (PRNP), account for 10-15% of cases. Genetic forms show a striking variability in their clinical and neuropathological picture and can sometimes mimic other neurodegenerative diseases.We report a novel PRNP mutation (V189I) in four CJD patients from three unrelated pedigrees. In three patients, the clinical features were typical for CJD and the diagnosis was pathologically confirmed, while the fourth patient presented with a complex phenotype including rapidly progressive dementia, behavioral abnormalities,
ataxia
and extrapyramidal features, and the diagnosis was probable CJD by current criteria, on the basis of PrP
Sc
detection in CSF by Real Time Quaking-Induced Conversion assay. In all the three patients with autopsy findings, the neuropathological analysis revealed diffuse synaptic type deposition of proteinase K-resistant prion protein (PrP
res
), and type 1 PrP
res
was identified in the brain by western blot analysis. So, the histopathological and biochemical profile associated with the V189I mutation was indistinguishable from the MM1/MV1 subtype of sporadic CJD.Our findings support a pathogenic role for the V189I PRNP variant, confirm the heterogeneity of the clinical phenotypes associated to PRNP mutations and highlight the importance of PrP
Sc
detection assays as diagnostic tools to unveil prion diseases presenting with atypical phenotypes.
...
PMID:Clinical and neuropathological phenotype associated with the novel V189I mutation in the prion protein gene. 3060 47
Creutzfeldt-Jakob disease (CJD) is a prion disease, usually presented with memory loss,
ataxia
, dementia, myoclonus, involuntary movements and psychiatric problems. D178N-homozygous 129M genotype has been recognized in the diagnosis of fatal familial insomnia (FFI) globally. Here we report a patient presented with progressive left upper limb stiffness, bradykinesia, hypomimia and weight loss (10 kg) initially. She progressed to dementia, dysphasia, dysphonia and be bedridden quickly but did not present insomnia. She was diagnosed with CJD corticobasal subtype carrying a classic D178N-129M mutation of
PRNP
in FFI. Remarkably, she has a strong family history of neurological degeneration diseases but the other members of this pedigree who do not carry D178N-homozygous 129M mutation in
PRNP
do not present any CJD or FFI symptoms. We conclude that this patient carrying D178N-homozygous 129M mutation in
PRNP
should be diagnosed as CJD. Thus, the clinicopathology should be considered as a crucial evidence in diagnosing some cases, but FFI could be evaluated as a differential diagnosis with a unique clinical profile.
List of abbreviations
AD: Alzheimer disease; ADL: Activities of Daily Living; CBD Cortical basal degeneration; CBS: Corticobasal syndrome; CJD: Creutzfeldt-Jakob disease; DWI: Diffusion-weighted image; EEG: Electroencephalograph, fCJD: familial
Creutzfeld-Jakob disease
; FFI: Fatal familial insomnia; FLAIR: Fluid-attenuated inversion recovery; MMSE: Mini-mental state examination; MoCA: Montreal Cognitive Assessment; MRI: Magnetic resonance imaging; PD: Parkinson disease; PrP: Prion protein; PSWC: Periodic sharp wave complexes; SWI: Susceptibility-weighted imaging.
...
PMID:Corticobasal manifestations of Creutzfeldt-Jakob disease with D178N-homozygous 129M genotype. 3294 18
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