Gerstmann‐Sträussler‐Scheinker disease with mutation at codon 102 and methionine at codon 129 of
            <i>PRNP</i>
            in previously unreported patients

Young, Katherine; Jones, Cheron; Piccardo, Pedro; Lazzarini, Alice; Golbe, Lawrence I.; Zimmerman, Thomas; Dickson, Dennis W.; McLachlan, D. Crapper; George‐Hyslop, Peter St; Lennox, Ashley L.; Perlman, S.; Vinters, Harry V.; Hodes, M. E.; Dlouhy, Stephen R.; Ghetti, Bernardino

doi:10.1212/wnl.45.6.1127

Cited by 41 publications

(26 citation statements)

References 2 publications

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“…Rather, GSS patients with CJD features are more likely to have PSIDDs [3,8,25,[42][43][44]. The EEG features of our patient 2 (IV-3) and patient 3 (V-2) at late disease stages corroborated this point of view.…”

Section: Discussionsupporting

confidence: 77%

“…P102L has also been documented in other families of different ethnicities [2,13,17,22,25,36,42,44] and is the most common mutation associated with GSS [8,9,11,17,21]. The disease is characterized pathologically by the deposition of multicentric amyloid-like plaques with a positive PrP immunoreactivity in the brain [4,27] and clinically by variable, progressive cerebellar ataxia or dementia in a relatively prolonged course (mean duration of illness: 5-7 years) [8,9,27].…”

Section: Introductionmentioning

confidence: 99%

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Transmissible spongiform encephalopathies with P102L mutation of PRNP manifesting different phenotypes: clinical, neuroimaging, and electrophysiological studies in Chinese kindred in Taiwan

Chi

Lee

et al. 2009

J Neurol

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A P102L point mutation in the prion protein gene (PRNP) usually causes Gerstmann-Sträussler-Scheinker disease (GSS), which is a rare hereditary transmissible spongiform encephalopathy (TSE). The clinical features include ataxia in 50s age group with subsequent dementia, spastic paraparesis and extrapyramidal signs. Many families have been reported from the Caucasian population, but only one from the Chinese. We hereby report a large Chinese family with P102L mutation of PRNP whose clinical manifestations at onset were intriguingly heterogeneous, either rapidly progressive dementia with scanty other neurological features or slowly progressive ataxia followed by cognitive impairment. The four-generation pedigree included eight patients with a mean age at onset of 36.9 +/- 12.9 (mean +/- SD) years. Mean disease duration to death in the four patients was 5.5 +/- 1.7 (mean +/- SD) years. Molecular analysis revealed a P102L mutation and M129 polymorphism in the PRNP gene in all affected individuals. TSE with P102L mutation of PRNP appears to have a remarkably variable phenotypic expressivity that may change with time and does not appear related to the codon 129 polymorphism.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Transmissible spongiform encephalopathies with P102L mutation of PRNP manifesting different phenotypes: clinical, neuroimaging, and electrophysiological studies in Chinese kindred in Taiwan

Chi

Lee

et al. 2009

J Neurol

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“…The proline to leucine change at codon 102 (P102L) was found in seven cases (17.5%). The P102L mutation is known to be the major cause of GSS worldwide (Hsiao et al 1989;Young et al 1995). The valine to isoleucine change at codon 210 (V210I) was detected in six cases of our group (15% of all cases with pathogenic mutations).…”

Section: Incidence Of Known Pathogenic Mutations In Germanymentioning

confidence: 66%

Molecular genetics of human prion diseases in Germany

et al. 1999

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Human prion diseases may be acquired as infectious diseases, they may be inherited in an autosomal dominant fashion or occur sporadically. Mutations and polymorphisms in the sequence of the coding region of the prion protein gene (PRNP) have been established as an important factor in all of these three types of prion diseases. Therefore, a total of 578 patients with suspect prion diseases referred to the German Creutzfeldt-Jakob disease (CJD) surveillance unit over a period of 4.5 years have been examined for mutations and polymorphisms in the coding region of PRNP. We found 40 cases with a missense mutation previously reported as pathogenic. Amongst these, the aspartate to asparagine change at codon 178 (D178N) was the most common mutation. All of these cases carried the D178N mutation in coupling with methionine at codon 129, resulting in the typical fatal familial insomnia (FFI) genotype. Most cases with pathogenic mutations were not found in the group of clinically "probable" cases according to established clinical criteria, supporting the notion that inherited prion diseases often exhibit atypical features. Two novel missense mutations (T188R and P238S) and several silent polymorphisms were found, demonstrating the quality of our screening procedure based on a modified version of the single-stranded conformational polymorphism technique. In "definite" CJD cases with no pathogenic mutation, the patients clinically classified as "probable" were mostly homozygous for methionine at the common polymorphism at codon 129, whereas there was a marked over-representation of patients homozygous for valine amongst those clinically classified as "possible". This large study on suspect cases of human prion diseases in Germany clearly shows that PRNP genetics is essential for a comprehensive analysis of prion diseases.

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“…In particular, both inherited forms and susceptibility to infections are associated with coding mutations and polymorphisms in the prion protein gene (Prnp) (Fig. 1) [10][11][12][13][14][15][16]. Prion strain types were also assessed as extremely influential in the controversial inter-species transmission of PrPDs [17].…”

Section: Introductionmentioning

confidence: 99%

The relationship between the 20S proteasomes and prion-mediated neurodegenerations: potential therapeutic opportunities

et al. 2010

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The dysfunction of cellular degradation pathways of aberrant and misfolded proteins is a critical event in the onset of neurodegenerative disorders. Among these pathologies, prion diseases are a unique class of transmissible fatal disorders affecting mammals, characterized by the presence of an abnormal isoform of a membrane-bound protein, namely the prion protein. The proteasome is the main proteolytic machinery in charge of removing damaged, oxidized and misfolded proteins and numerous authors have approached the involvement of this complex in the prion protein cellular processing. Herein, we described the general features of prion disorders focusing our attention on the available data on the interplay between the infectious agent and the proteasome system, exploring its implications in prion-mediated toxicity. Finally, considering the proteasome as a potential drug target, we reviewed possible therapeutic opportunities in the treatment of such pathologies.

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Gerstmann‐Sträussler‐Scheinker disease with mutation at codon 102 and methionine at codon 129 of PRNP in previously unreported patients

Cited by 41 publications

References 2 publications

Transmissible spongiform encephalopathies with P102L mutation of PRNP manifesting different phenotypes: clinical, neuroimaging, and electrophysiological studies in Chinese kindred in Taiwan

Transmissible spongiform encephalopathies with P102L mutation of PRNP manifesting different phenotypes: clinical, neuroimaging, and electrophysiological studies in Chinese kindred in Taiwan

Molecular genetics of human prion diseases in Germany

The relationship between the 20S proteasomes and prion-mediated neurodegenerations: potential therapeutic opportunities

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