ArticleAmerican journal of human genetics2014
Parental somatic mosaicism is underrecognized and influences recurrence risk of genomic disorders.
Article in American journal of human genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers, 2 of them syntheses that pooled it.
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Who cites it
153 citing papers in PubMed, 2 syntheses or guidelines pooled it, 279 citations in OpenAlex.
- Genomic mosaicism in colorectal cancer and polyposis syndromes: a systematic review and meta-analysis.International journal of colorectal disease · 2024Pooled it
- Characterization of large structural genetic mosaicism in human autosomes.American journal of human genetics · 2015Pooled it
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- A distributive germline restricts the spread of new mutations.bioRxiv : the preprint server for biology · 2026Article
- Identification of a De Novo MAGEL2 Pathogenic Variant in Schaaf-Yang Syndrome and the Importance of Paternal Allele Confirmation.Journal of clinical laboratory analysis · 2026Article
- Genetic Variants in Recurrent Euploid Pregnancy Loss.medRxiv : the preprint server for health sciences · 2025Article
- Comprehensive benchmarking of somatic structural variant detection at ultra-low allele fractions.bioRxiv : the preprint server for biology · 2025Article
- Bullous Congenital Ichthyosiform Erythroderma with Tinea Capitis in Half-Siblings: Rare Phenomenon in Ichthyosis with Co-ExistingBiomedicines · 2025Article
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- Sequence diversity lost in early pregnancy.Nature · 2025Article
- A review of APC somatic mosaicism and specific APC variants - I1307K and promotor variants.Familial cancer · 2025Review
- Germline mosaicism in TCF20-associated neurodevelopmental disorders: a case study and literature review.Journal of human genetics · 2025Review
- The clinical application and challenges of preimplantation genetic testing.Frontiers in genetics · 2025Review
- A family-based approach to cascade genetic testing in a pediatric cancer genetics clinic.Familial cancer · 2024Article
- Transgenerational transmission of post-zygotic mutations suggests symmetric contribution of first two blastomeres to human germline.Nature communications · 2024Article
- Human embryonic genetic mosaicism and its effects on development and disease.Nature reviews. Genetics · 2024Review
- Expanding the Spectrum of Autosomal DominantGenes · 2024Review
- Transgenerational transmission of post-zygotic mutations suggests symmetric contribution of first two blastomeres to human germline.bioRxiv : the preprint server for biology · 2024Article
- [Sperm Mosaic Variants and Their Influence on the Offspring].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Review
93 more citing papers are in PubMed but not listed here.
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Authors and funding
28 authors at 7 institutions in 5 countries.
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Abstract
New human mutations are thought to originate in germ cells, thus making a recurrence of the same mutation in a sibling exceedingly rare. However, increasing sensitivity of genomic technologies has anecdotally revealed mosaicism for mutations in somatic tissues of apparently healthy parents. Such somatically mosaic parents might also have germline mosaicism that can potentially cause unexpected intergenerational recurrences. Here, we show that somatic mosaicism for transmitted mutations among parents of children with simplex genetic disease is more common than currently appreciated. Using the sensitivity of individual-specific breakpoint PCR, we prospectively screened 100 families with children affected by genomic disorders due to rare deletion copy-number variants (CNVs) determined to be de novo by clinical analysis of parental DNA. Surprisingly, we identified four cases of low-level somatic mosaicism for the transmitted CNV in DNA isolated from parental blood. Integrated probabilistic modeling of gametogenesis developed in response to our observations predicts that mutations in parental blood increase recurrence risk substantially more than parental mutations confined to the germline. Moreover, despite the fact that maternally transmitted mutations are the minority of alleles, our model suggests that sexual dimorphisms in gametogenesis result in a greater proportion of somatically mosaic transmitting mothers who are thus at increased risk of recurrence. Therefore, somatic mosaicism together with sexual differences in gametogenesis might explain a considerable fraction of unexpected recurrences of X-linked recessive disease. Overall, our results underscore an important role for somatic mosaicism and mitotic replicative mutational mechanisms in transmission genetics.
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