ReviewInternational journal of legal medicine2026
Molecular autopsy in unexplained sudden death: a systematic review and meta-analysis of ACMG-corrected diagnostic yield, genomic architecture, and family translation.
Review in International journal of legal medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMolecular autopsy is increasingly used in unexplained sudden death, but reported diagnostic yield varies across sequencing eras, cohort types, and variant-classification frameworks. This review evaluated ACMG-corrected diagnostic yield, genomic architecture, VUS burden, and downstream family translation.
methodsThis PRISMA-based systematic review and meta-analysis was registered in PROSPERO (CRD420251082728). Studies reporting postmortem genetic testing in sudden unexplained death were included. Quantitative diagnostic-yield synthesis included 44 core molecular autopsy studies comprising 4,041 index cases; 35 studies contributed family-translation data. Random-effects meta-analysis was performed, and subgroup analyses were conducted by sequencing strategy and age group.
resultsThe pooled ACMG-corrected diagnostic yield was approximately 13%, with substantial heterogeneity. Broader sequencing approaches showed modestly higher yield than candidate/restricted panels (OR 1.36, 95% CI 1.09-1.70; p = 0.006), but with greater VUS burden. Young adult/adult cohorts showed the highest pooled yield, while infant/pediatric cohorts demonstrated broader multisystem genomic architecture and higher VUS burden. Recurrent substrates included RYR2, SCN5A, KCNQ1, KCNH2, TTN, and MYBPC3. Family-translation data were available from 35 studies, including 25 overlapping index-case cohorts; genotype-positive relatives, phenotype-positive relatives, segregation analysis, and clinically actionable interventions were frequently reported.
conclusionsContemporary ACMG-compatible molecular autopsy provides modest but clinically meaningful diagnostic yield. Its major value extends beyond postmortem diagnosis, supporting family-based preventive genomic medicine through cascade screening, phenotype correlation, and targeted risk stratification.
Indexed as
Identifiers
42538417What OpenQuestion holds
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.