ArticleHuman genomics2021
Detection of low-level parental somatic mosaicism for clinically relevant SNVs and indels identified in a large exome sequencing dataset.
Article in Human genomics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 29 citations in OpenAlex.
- Somatic mosaicism and skewed X-chromosome inactivation associated with male-pattern choroideremia phenotype in a female patient.Documenta ophthalmologica. Advances in ophthalmology · 2026Article
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- Molecular Characterization ofHuman mutation · 2026Article
- Suspected parental gonadal/gonadosomatic mosaicism for a TINF2 mutation in two sisters with dyskeratosis congenita.Frontiers in genetics · 2026Article
- Parental Somatic Mosaicism Detected During Prenatal Diagnosis.Prenatal diagnosis · 2025Article
- Human embryonic genetic mosaicism and its effects on development and disease.Nature reviews. Genetics · 2024Review
- Genomic Mosaicism of the Brain: Origin, Impact, and Utility.Neuroscience bulletin · 2024Review
- Subclonal Cancer Driver Mutations Are Prevalent in the Unresected Peritumoral Edema of Adult Diffuse Gliomas.Cancer research · 2024Article
- Review
- Exome sequencing improves the molecular diagnostics of paediatric unexplained neurodevelopmental disorders.Orphanet journal of rare diseases · 2024Article
- The contribution of mosaicism to genetic diseases and de novo pathogenic variants.American journal of medical genetics. Part A · 2023Article
- Detection of gonosomal mosaicism by ultra-deep sequencing and droplet digital PCR in patients with Emery-Dreifuss muscular dystrophy.Molecular genetics & genomic medicine · 2023Article
- Maternal mosaicism in SSBP1 causing optic atrophy with retinal degeneration: implications for genetic counseling.Orphanet journal of rare diseases · 2023Article
- Maternal Mosaicism in SSBP1 Causing Optic Atrophy with Retinal Degeneration: Implications for Genetic Counseling.Research square · 2023Article
- Quantitative assessment of low-level parental mosaicism of SNVs and CNVs in Waardenburg syndrome.Human genetics · 2023Article
- Parental mosaicism for apparent de novo genetic variants: Scope, detection, and counseling challenges.Prenatal diagnosis · 2022Review
- Analysis of trio test in neurodevelopmental disorders.Frontiers in pediatrics · 2022Article
- Incomplete Penetrance and Variable Expressivity: From Clinical Studies to Population Cohorts.Frontiers in genetics · 2022Review
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundDue to the limitations of the current routine diagnostic methods, low-level somatic mosaicism with variant allele fraction (VAF) < 10% is often undetected in clinical settings. To date, only a few studies have attempted to analyze tissue distribution of low-level parental mosaicism in a large clinical exome sequencing (ES) cohort.
methodsUsing a customized bioinformatics pipeline, we analyzed apparent de novo single-nucleotide variants or indels identified in the affected probands in ES trio data at Baylor Genetics clinical laboratories. Clinically relevant variants with VAFs between 30 and 70% in probands and lower than 10% in one parent were studied. DNA samples extracted from saliva, buccal cells, redrawn peripheral blood, urine, hair follicles, and nail, representing all three germ layers, were tested using PCR amplicon next-generation sequencing (amplicon NGS) and droplet digital PCR (ddPCR).
resultsIn a cohort of 592 clinical ES trios, we found 61 trios, each with one parent suspected of low-level mosaicism. In 21 parents, the variants were validated using amplicon NGS and seven of them by ddPCR in peripheral blood DNA samples. The parental VAFs in blood samples varied between 0.08 and 9%. The distribution of VAFs in additional tissues ranged from 0.03% in hair follicles to 9% in re-drawn peripheral blood.
conclusionsOur study illustrates the importance of analyzing ES data using sensitive computational and molecular methods for low-level parental somatic mosaicism for clinically relevant variants previously diagnosed in routine clinical diagnostics as apparent de novo.
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