Evidence map›Paper›PMID 41256127›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Mortality of individuals with antemortem genetic testing for

Yuan Lian, Keisi Kotobelli, Kathleen Glisic, Daniel A Sprague, Sonia M Vallabh, Brian S Appleby, Eric Vallabh Minikel

Registry-linked trialAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07732608 (PROSPECT), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07732608 not yet recruitingnot on this mapstarted 2026, after this paper: background citation

PROSPECT: A Registry and Longitudinal Natural History Study of Individuals at Risk for Genetic Prion Disease

Typeobservational_patient_registrySponsorUniversity Hospitals Cleveland Medical CenterRan2026 to 2036Enrolled1,000ConditionsPrion Diseases
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Yuan LianProgram in Brain Health, Broad Institute of MIT and Harvard, Cambridge, MA 02142.
Keisi KotobelliNational Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, OH, 44106, USA.
Kathleen GlisicNational Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, OH, 44106, USA.
Daniel A SpragueProgram in Brain Health, Broad Institute of MIT and Harvard, Cambridge, MA 02142.
Sonia M VallabhProgram in Brain Health, Broad Institute of MIT and Harvard, Cambridge, MA 02142.ORCID 0000-0003-3824-2702
Brian S ApplebyNational Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, OH, 44106, USA.
Eric Vallabh MinikelProgram in Brain Health, Broad Institute of MIT and Harvard, Cambridge, MA 02142.ORCID 0000-0003-2206-1608

Funding

Biomarkers and Mechanisms of PrP Misfolding, Mutation, and DeficiencyR01NS132022 · NINDS · BROAD INSTITUTE, INC. · PI Eric Vallabh Minikel · 2024 to 2026
$1.9M
NINDS NIH HHS R01 NS132022
6 · The paper itself

Abstract

Objectives: To characterize the survival of individuals with pathogenic Methods: In this single center cohort study, we gathered data on individuals who received positive antemortem Results: 404 individuals received positive genetic test results. Of 206 cases symptomatic at the time of genetic testing, 188 are likely now deceased based on typical disease duration for their genetic variants. Combined autopsy and public record searches in combination confirmed 174 of these deaths, for an estimated sensitivity of 92.6%. Of 111 autopsied individuals, evidence of death was found in public record searches for 109, a sensitivity of 98.2%. Of 198 individuals who were asymptomatic at the time of testing, 32 since died of definite or possible prion disease. Among 20 of these who underwent autopsy, public record searches confirmed deaths of 18, for a sensitivity of 90%. Among 99 E200K individuals over 936 person-years of follow-up, 18 deaths were observed, significantly fewer than 27.4 expected according to life tables based on retrospective data. The age-dependent penetrance of E200K calculated from prospective data was significantly lower than that from retrospective data, with 69% penetrance by age 80 and a median age at death of 75. No significant difference was found for D178N, which appears highly penetrant, though the median age at death was numerically higher than seen in retrospective data. V210I was associated with just 2 deaths, both after age 90, consistent with minimal penetrance. Discussion: These data support the accuracy of penetrance classifications for Clinical Trials Registration: Not applicable.

Identifiers

PMID41256127
PMCPMC12622085

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.