ArticlePLoS genetics2025
Parental germline mosaicism in genome-wide phased de novo variants: Recurrence risk assessment and implications for precision genetic counselling.
Article in PLoS genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04564235 (Risk of Recurrence of de Novo Mutations), which is not on this map. Cited by 4 papers.
What it found
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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.
Risk of Recurrence of de Novo Mutations: Research and Quantification of Paternal Germinal Mosaicism by the Combined Use of Genomic Tools
Who cites it
4 citing papers in PubMed.
- A Novel De Novo MTM1 Insertion Frameshift Variant Causes X-Linked Myotubular Myopathy in a Chinese Female.Molecular genetics & genomic medicine · 2026Article
- Article
- A Synonymous DLG4 Variant (c.771G>A) Causes Exon 9 Skipping via Paternal Germline Mosaicism in DLG4-Related Synaptopathy.Molecular genetics & genomic medicine · 2026Article
- Complete Androgen Insensitivity Syndrome (CAIS) Genetic Counseling: Navigating Germline Mosaicism Concerns.Case reports in genetics · 2026Article
Corrections and comments
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Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
De novo mutations (DNMs) have a significant impact on human health, notably through their contribution to developmental disorders. DNMs occur in both paternal and maternal germlines via diverse mechanisms, including parental early embryonic mosaicism, at high recurrence risk for subsequent pregnancies through germline mosaicism. This phenomenon has been studied mostly on isolated pathogenic variants, but its contribution to genome-wide phased variants in individual genomes is underexplored. We aimed to categorize DNMs and their recurrence risk by detecting and phasing a large set of DNMs via short- and long-read genome sequencing followed by systematic deep sequencing of parental blood and sperm DNA. We detected an average of 85.6 DNM per trio (n=5 trios), with an expected paternal bias of 80%. Targeted resequencing of parental blood and sperm (depth>5000x) revealed 20/334 parental germline mosaics (2-5 per trio) with variant allele fractions (VAFs) ranging from 0.24% to 14.7%, including 7 that were detected in paternal sperm exclusively (1-2 per trio). Owing to paternal bias, maternally phased variants were 3.4x more likely to be mosaic in blood. VAF in sperm samples was used as an indicator for the risk of recurrence of paternally phased DNM. Fourteen variants (out of 244, 5.7%) exhibited detectable sperm mosaicism, while the remaining 230 showed no evidence of mosaicism. Sperm sequencing therefore enabled a precise quantification of the recurrence risk of most individual DNMs. We predict that the use of long-read genome sequencing in genomic medicine will enable the critical step of variant phasing, improving the genetic counselling of rare diseases mediated by DNMs.
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