A new point mutation of the prion protein gene in Creutzfeldt-Jakob disease (original) (raw)
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Journal of the …, 1999
A point mutation at codon 210 of the prion protein gene (PRNP), resulting in the substitution of isoleucine for valine (V210I) has been found in a 54-year-old Moroccan patient affected with Creutzfeldt-Jakob disease (CJD). This patient is the first carrier of the PRNP V210I mutation reported from North Africa. The clinical presentation of the patient was rather similar to that seen in classical CJD, except that unusual early sensory symptoms were observed. The mother of the proband, aged 72, is a further example of an asymptomatic elderly carrier of the PRNP V210I mutation, suggesting an incomplete penetrance of the disease.
Arquivos de Neuro-Psiquiatria, 2001
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.
Novel Prion Protein Gene Mutation in an Octogenarian With Creutzfeldt-Jakob Disease
Archives of Neurology, 2000
Background: The transmissible spongiform encephalopathies constitute a fascinating and biologically unique group of invariably fatal neurodegenerative disorders that affect both animals and humans. Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia represent the more common human phenotypes. Excluding the small number of iatrogenically transmitted cases, approximately 85% to 90% of patients develop CJD without identifiable explanation, with an increasing number of different mutations in the prion protein gene (PRNP) recognized as probably causative in the remainder. Objective: To report on an 82-year-old woman with pathologically confirmed CJD found unexpectedly to harbor a novel mutation in PRNP. Methods: Routine clinical investigations were undertaken to elucidate the cause of the rapidly progressive dementia and neurological decline manifested by the patient, including magnetic resonance imaging of the brain, electroencephalography, and cerebrospinal fluid analysis for the 14-3-3  protein. Standard postmortem neuropathological examination of the brain was performed, including immunocytochemistry of representative sections to detect the prion protein. Posthumous genetic analysis of the open reading frame of PRNP was performed on frozen brain tissue using polymerase chain reaction and direct sequencing.
[A case of Creutzfeldt-Jakob disease with a point mutation of prion protein at codon 180]
Nō to shinkei = Brain and nerve, 2004
A 67-year-old woman was admitted to our hospital with progressive aphasia. There was no family history of similar diseases or any history of dura transplantation. Cranial magnetic resonance imaging (MRI) showed high signal areas in the temporal and parietal cortex predominantly on the left side on both T2-weighted images and on diffusion-weighted images. There were no periodic synchronous discharges observed on the electroencephalogram. As prion protein gene codon 180 point mutation (Val/Ile) was detected, we diagnosed her as having Creutzfeldt-Jakob disease (CJD). The characteristics of CJD of this type differ from those of sporadic CJD. To date, few papers on CJD with point mutation of codon 180 have been reported from Japan.
Dementia e Neuropsychologia
Genetic Creutzfeldt-Jakob disease (gCJD) represents less than 15% of CJD cases, and its clinical picture may be either indistinguishable from that of sporadic CJD (sCJD) or be atypical, usually with younger onset and longer duration. We report a case of 59-year old Brazilian man who presented rapidly progressive cognitive decline and cerebellar ataxia. EEG revealed periodic activity. A brother and a cousin of the patient had CJD. A point mutation at codon 200 (E200K) of the prion protein gene (PRNP) was found and death occurred 11 months after onset of symptoms. Autopsy was not performed. The clinical presentation of gCJD associated with E200K, which is the most frequent PRNP mutation, is quite similar to sCDJ. This is the fi rst report of E200K mutation in Brazil, and it is possible that a more systematic search for its occurrence may show it to be relatively frequent in Brazil. Doença de Creutzfeldt-Jakob associada com mutação de ponto no códon 200 do gene da proteína príon no Bra...
Journal of Neurology, Neurosurgery & Psychiatry, 1995
A case of familial Creutzfeldt-Jakob disease associated with a 144 base pair insertion in the-open reading frame of the prion protein gene is described. Sequencing of the mutated allele showed an arrangement of-six octapeptide repeats, distinct from that of a recently described British family with an insertion of similar size. Thirteen years previously the brother of the proband had died from "Huntington's disease", but re-examination of his neuropathology revealed spongiform encephalopathy and antiprion protein immunocytochemistry gave a positive result. The independent evolution of at least two distinct pathological 144 base pair insertions in Britain is proposed. The importance of maintaming a high index of suspicion of inherited Creutzfeldt-Jakob disease in cases of familial neurodegenerative disease is stressed. (J Neurol Neurosurg Psychiatry 1995;58:65-69)
Acta Neuropathologica Communications
The methionine (M)—valine (V) polymorphic codon 129 of the prion protein gene (PRNP) plays a central role in both susceptibility and phenotypic expression of sporadic Creutzfeldt-Jakob diseases (sCJD). Experimental transmissions of sCJD in humanized transgenic mice led to the isolation of five prion strains, named M1, M2C, M2T, V2, and V1, based on two major conformations of the pathological prion protein (PrPSc, type 1 and type 2), and the codon 129 genotype determining susceptibility and propagation efficiency. While the most frequent sCJD strains have been described in codon 129 homozygosis (MM1, MM2C, VV2) and heterozygosis (MV1, MV2K, and MV2C), the V1 strain has only been found in patients carrying VV. We identified six sCJD cases, 4 in Catalonia and 2 in Italy, carrying MV at PRNP codon 129 in combination with PrPSc type 1 and a new clinical and neuropathological profile reminiscent of the VV1 sCJD subtype rather than typical MM1/MV1. All patients had a relatively long durati...
Familial Creutzfeldt-Jakob disease with a novel 120-bp insertion in the prion protein gene
Annals of Neurology, 1999
The clinical course, neuropathological features, and genetic findings in 3 members of a German family carrying a novel 120-bp insertion in the prion protein (PrP) gene are described. Genetic analysis of the mutated allele revealed a sequence of five extra octapeptide repeats, distinct from those of the two previously reported families with an insertion of this size. There was distinctive variation in the clinical course and the onset and duration of the illness in the documented subjects. Neuropathological evaluation showed neuronal loss and gliosis in the neocortex of the 3 examined cases; spongiform degeneration was found in 2 of them. PrP immunoreactivity of unusual morphology and distinct distribution was present in the cerebellum and neocortex ("blurred staining") of 2 examined cases. One subject showed features usually found in sporadic Creutzfeldt-Jakob disease with a punctate type of PrP deposition in the cerebellum. In addition, there were some plaque-like PrP aggregates morphologically similar to the other 2 cases in the molecular layer of the cerebellum, and unusual PrP immunoreactivity ("fleecy staining") was found in the neocortex. The clinicopathological heterogeneity in the documented family is in accordance with the phenotypic variability associated with previously reported insertions.