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Homozygous R136S mutation in PRNP gene causes inherited early onset prion disease

Overview of attention for article published in Alzheimer's Research & Therapy, October 2021
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (83rd percentile)
  • Average Attention Score compared to outputs of the same age and source

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1 news outlet
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Title
Homozygous R136S mutation in PRNP gene causes inherited early onset prion disease
Published in
Alzheimer's Research & Therapy, October 2021
DOI 10.1186/s13195-021-00912-6
Pubmed ID
Authors

Teresa Ximelis, Alba Marín-Moreno, Juan Carlos Espinosa, Hasier Eraña, Jorge M. Charco, Isabel Hernández, Carmen Riveira, Daniel Alcolea, Eva González-Roca, Iban Aldecoa, Laura Molina-Porcel, Piero Parchi, Marcello Rossi, Joaquín Castilla, Raquel Ruiz-García, Ellen Gelpi, Juan María Torres, Raquel Sánchez-Valle

Abstract

More than 40 pathogenic heterozygous PRNP mutations causing inherited prion diseases have been identified to date. Recessive inherited prion disease has not been described to date. We describe the clinical and neuropathological data of inherited early-onset prion disease caused by the rare PRNP homozygous mutation R136S. In vitro PrPSc propagation studies were performed using recombinant-adapted protein misfolding cyclic amplification technique. Brain material from two R136S homozygous patients was intracranially inoculated in TgMet129 and TgVal129 transgenic mice to assess the transmissibility of this rare inherited form of prion disease. The index case presented symptoms of early-onset dementia beginning at the age of 49 and died at the age of 53. Neuropathological evaluation of the proband revealed abundant multicentric PrP plaques and Western blotting revealed a ~ 8 kDa protease-resistant, unglycosylated PrPSc fragment, consistent with a Gerstmann-Sträussler-Scheinker phenotype. Her youngest sibling suffered from progressive cognitive decline, motor impairment, and myoclonus with onset in her late 30s and died at the age of 48. Genetic analysis revealed the presence of the R136S mutation in homozygosis in the two affected subjects linked to homozygous methionine at codon 129. One sibling carrying the heterozygous R136S mutation, linked to homozygous methionine at codon 129, is still asymptomatic at the age of 74. The inoculation of human brain homogenates from our index case and an independent case from a Portuguese family with the same mutation in transgenic mice expressing human PrP and in vitro propagation of PrPSc studies failed to show disease transmissibility. In conclusion, biallelic R136S substitution is a rare variant that produces inherited early-onset human prion disease with a Gerstmann-Sträussler-Scheinker neuropathological and molecular signature. Even if the R136S variant is predicted to be "probably damaging", heterozygous carriers are protected, at least from an early onset providing evidence for a potentially recessive pattern of inheritance in human prion diseases.

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The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 18 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 18 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 3 17%
Student > Bachelor 2 11%
Researcher 2 11%
Professor 1 6%
Unspecified 1 6%
Other 1 6%
Unknown 8 44%
Readers by discipline Count As %
Neuroscience 3 17%
Medicine and Dentistry 2 11%
Biochemistry, Genetics and Molecular Biology 2 11%
Unspecified 1 6%
Unknown 10 56%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 October 2021.
All research outputs
#3,023,999
of 23,310,485 outputs
Outputs from Alzheimer's Research & Therapy
#746
of 1,268 outputs
Outputs of similar age
#69,750
of 439,396 outputs
Outputs of similar age from Alzheimer's Research & Therapy
#28
of 49 outputs
Altmetric has tracked 23,310,485 research outputs across all sources so far. Compared to these this one has done well and is in the 86th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,268 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 25.9. This one is in the 37th percentile – i.e., 37% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 439,396 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 83% of its contemporaries.
We're also able to compare this research output to 49 others from the same source and published within six weeks on either side of this one. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.