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Biallelic Loss of Function of SORL1 in an Early Onset Alzheimer’s Disease Patient

Overview of attention for article published in Journal of Alzheimer's Disease, February 2018
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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 (80th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (59th percentile)

Mentioned by

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1 news outlet
twitter
1 tweeter

Citations

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2 Dimensions

Readers on

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10 Mendeley
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Title
Biallelic Loss of Function of SORL1 in an Early Onset Alzheimer’s Disease Patient
Published in
Journal of Alzheimer's Disease, February 2018
DOI 10.3233/jad-170981
Pubmed ID
Authors

Kilan Le Guennec, Hélène Tubeuf, Didier Hannequin, David Wallon, Olivier Quenez, Stéphane Rousseau, Anne-Claire Richard, Jean-François Deleuze, Anne Boland, Thierry Frebourg, Pascaline Gaildrat, Dominique Campion, Alexandra Martins, Gaël Nicolas

Abstract

Heterozygous SORL1 protein truncating variants (PTV) are a strong risk factor for early-onset Alzheimer's disease (EOAD). In case control studies performed at the genome-wide level, PTV definition is usually straightforward. Regarding splice site variants, only those affecting canonical sites are typically included. Some other variants, not annotated as PTV, could, however, affect splicing and hence result in a loss of SORL1 function. We took advantage of the whole exome sequencing data from the 9/484 patients with a previously reported SORL1 PTV in the French EOAD series and searched for a second variant which may affect splicing and eventually result in more than 50% loss of function overall. We found that one patient, known to carry a variant predicted to disrupt the canonical 5' splice site of exon 8, also carried a second novel intronic variant predicted to affect SORL1 splicing of exon 29. Segregation analysis showed that the second variant was located in trans from the known PTV. We performed ex vivo minigene splicing assays and showed that both variants led to the generation of transcripts containing a premature stop codon. This is therefore the first evidence of a human carrying biallelic SORL1 PTV. This patient had a family history of dementia in both maternal and paternal lineages with later ages of onset than the proband himself. However, his 55 years age at onset was in the same ranges as previously published SORL1 heterozygous PTV carriers. This suggests that biallelic loss of SORL1 function is an extremely rare event that was not associated with a dramatically earlier age at onset than heterozygous SORL1 loss-of-function variant carriers, in this single patient.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 10 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 10 100%

Demographic breakdown

Readers by professional status Count As %
Unspecified 3 30%
Student > Ph. D. Student 2 20%
Researcher 2 20%
Student > Doctoral Student 1 10%
Other 1 10%
Other 1 10%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 4 40%
Unspecified 3 30%
Agricultural and Biological Sciences 1 10%
Psychology 1 10%
Medicine and Dentistry 1 10%
Other 0 0%

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 07 June 2018.
All research outputs
#1,516,848
of 13,044,924 outputs
Outputs from Journal of Alzheimer's Disease
#1,034
of 3,715 outputs
Outputs of similar age
#52,156
of 270,510 outputs
Outputs of similar age from Journal of Alzheimer's Disease
#51
of 145 outputs
Altmetric has tracked 13,044,924 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,715 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 16.3. This one has gotten more attention than average, scoring higher than 68% of its peers.
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 270,510 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 80% of its contemporaries.
We're also able to compare this research output to 145 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 59% of its contemporaries.