A prion-linked psychiatric disorder

Samaia, H. B.; Mari, Jair de Jesus; Vallada, Homero; Moura, Ricardo P.; Simpson, Andrew J.G.; Brentani, Helena

doi:10.1038/36757

Cited by 53 publications

(24 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The high absolute and proportionate incidence of the V210I mutation in Italy is striking; most affected families lived in three adjacent areas (Ladogana et al 2005b). It is a pertinent point that a single report on the N171S mutation suggested a psychiatric phenotype, whereas in our series this mutation was associated with CJD (Samaia et al 1997 the availability of genetic data. Focal accumulations of genetic patients (Mayer et al 1977) may be due to genetic isolation but the explanation for the overall intercountry variability in this study is uncertain.…”

Section: Discussionmentioning

confidence: 58%

Genetic prion disease: the EUROCJD experience

Kovács¹,

et al. 2005

View full text Add to dashboard Cite

A total of 10-15% of human transmissible spongiform encephalopathies (TSEs) or prion diseases are characterised by disease-specific mutations in the prion protein gene (PRNP). We examined the phenotype, distribution, and frequency of genetic TSEs (gTSEs) in different countries/geographical regions. We collected standardised data on gTSEs between 1993 and 2002 in the framework of the EUROCJD collaborative surveillance project. Our results show that clinicopathological phenotypes include genetic Creutzfeldt-Jakob disease (gCJD), fatal familial insomnia (FFI), and Gerstmann-Sträussler-Scheinker disease (GSS). Genetic TSE patients with insert mutation in the PRNP represent a separate group. Point and insertional mutations in the PRNP gene varies significantly in frequency between countries. The commonest mutation is E200K. Absence of a positive family history is noted in a significant proportion of cases in all mutation types (12-88%). FFI and GSS patients develop disease earlier than gCJD. Base pair insertions associated with the Creutzfeldt-Jakob disease (CJD) phenotype, GSS, and FFI cases have a longer duration of illness compared to cases with point mutations and gCJD. Cerebrospinal fluid 14-3-3 immunoassay, EEG, and MRI brain scan are useful in the diagnosis of CJD with point mutations, but are less sensitive in the other forms. Given the low prevalence of family history, the term "gTSE" is preferable to "familial TSE". Application of genetic screening in clinical practice has the advantage of early diagnosis and may lead to the identification of a risk of a TSE.

show abstract

Section: Discussionmentioning

confidence: 58%

Genetic prion disease: the EUROCJD experience

Kovács¹,

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Mutations at codons 102 (Pro-Leu), 117 (Ala-Val), 198 (Phe-Ser) and 217 (Gln-Arg) are found in patients with GSS, while 178 (Asp-Asn), 200 (Glu-Lys), 208 (Arg-His) and 210 (Val-Ile) are found in patients with familial CJD (24). Fatal familial insomnia patients presented mutation at codon 178 (Asp-Asn) (25) and mutation at residue 171 has been observed by our group in one family suffering from severe psychiatric disorders (26). Moreover, a polymorphism at codon 129 appears to increase susceptibility to iatrogenic CJD (24).…”

Section: Human Prion Diseasesmentioning

confidence: 95%

A receptor for infectious and cellular prion protein

Martins

1999

Braz J Med Biol Res

View full text Add to dashboard Cite

Prions are an unconventional form of infectious agents composed only of protein and involved in transmissible spongiform encephalopathies in humans and animals. The infectious particle is composed by PrPsc which is an isoform of a normal cellular glycosyl-phosphatidylinositol (GPI) anchored protein, PrPc, of unknown function. The two proteins differ only in conformation, PrPc is composed of 40% a helix while PrPsc has 60% ß-sheet and 20% a helix structure. The infection mechanism is trigged by interaction of PrPsc with cellular prion protein causing conversion of the latters conformation. Therefore, the infection spreads because new PrPsc molecules are generated exponentially from the normal PrPc. The accumulation of insoluble PrPsc is probably one of the events that lead to neuronal death. Conflicting data in the literature showed that PrPc internalization is mediated either by clathrin-coated pits or by caveolae-like membranous domains. However, both pathways seem to require a third protein (a receptor or a prion-binding protein) either to make the connection between the GPI-anchored molecule to clathrin or to convert PrPc into PrPsc. We have recently characterized a 66-kDa membrane receptor which binds PrPc in vitro and in vivo and mediates the neurotoxicity of a human prion peptide. Therefore, the receptor should have a role in the pathogenesis of prion-related diseases and in the normal cellular process. Further work is necessary to clarify the events triggered by the association of PrPc/PrPsc with the receptor.

show abstract

“…The prominent symptoms were different psychiatric features (depression, delusion, hallucination, schizophrenia, schizoaffective disorders). Samaia et al [25 ]summarized a new causally linked mutation with a psychiatric featured phenotype. In contradiction Tsai et al [26] tested a large group of patients (n = 234) with familial schizophrenia, non-familial schizophrenia and healthy controls and did not find the N171S mutation in PRNP ; nonetheless, an association between the mutation and the disease was not excluded by this analysis.…”

Section: Discussionmentioning

confidence: 99%

Report about Four Novel Mutations in the Prion Protein Gene

Schelzke

Stoeck

Eigenbrod

et al. 2013

Dement Geriatr Cogn Disord

View full text Add to dashboard Cite

Background/Aims: Since detection of the prion protein gene (PRNP) more than 30 mutations have been discovered. Some have only been found in single case reports without known intrafamilial accumulation or neuropathological proof so that the causal connection between mutation and disease could not be proved. Those patients often present atypical clinical phenotypes, and it is not unusual that they are classified as diseases other than Creutzfeldt-Jakob disease (CJD). Methods: Cases of suspected CJD have been reported to the national reference center for prion diseases. Clinical and diagnostic data were collected, and a classification of definite, possible or probable prion disease was made. Molecular analysis of PRNP was performed by capillary sequencing. Results: We have described 4 cases with atypical clinical and diagnostic findings and unknown mutations in PRNP so far. Conclusion: Three patients fulfilled the criteria of probable CJD, and 1 patient fulfilled the criteria of possible CJD but the clinical picture in none of the patients was typical CJD; hence, it remained questionable whether the mutations were causal of the disease.

show abstract

A prion-linked psychiatric disorder

Cited by 53 publications

References 0 publications

Genetic prion disease: the EUROCJD experience

Genetic prion disease: the EUROCJD experience

A receptor for infectious and cellular prion protein

Report about Four Novel Mutations in the Prion Protein Gene

Contact Info

Product

Resources

About