ArticleGenome medicine2019
A clinical survey of mosaic single nucleotide variants in disease-causing genes detected by exome sequencing.
Article in Genome medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Clinical relevance of mosaic variants detected by exome sequencing.The Journal of allergy and clinical immunology · 2026Article
- Expanding the clinical and molecular spectrum of Schaaf-Yang syndrome in China: evidence for a severe phenotypic subgroup associated withFrontiers in cell and developmental biology · 2026Article
- Parental Somatic Mosaicism Detected During Prenatal Diagnosis.Prenatal diagnosis · 2025Article
- Next-generation phenotyping integrated in a national framework for patients with ultrarare disorders improves genetic diagnostics and yields new molecular findings.Nature genetics · 2024Article
- Assessment of parental mosaicism rates in neurodevelopmental disorders caused by apparent de novo pathogenic variants using deep sequencing.Scientific reports · 2024Article
- Functional genomics and small molecules in mitochondrial neurodevelopmental disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Revealing parental mosaicism: the hidden answer to the recurrence of apparent de novo variants.Human genomics · 2023Article
- Clinical case report: mosaicCold Spring Harbor molecular case studies · 2023Article
- SNV/indel hypermutator phenotype in biallelic RAD51C variant: Fanconi anemia.Human genetics · 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
- Identification and characterisation of de novo germline structural variants in two commercial pig lines using trio-based whole genome sequencing.BMC genomics · 2023Article
- Patterns of mosaicism for sequence and copy-number variants discovered through clinical deep sequencing of disease-related genes in one million individuals.American journal of human genetics · 2023Article
- SNV/indel hypermutator phenotype in biallelic RAD51C variant - Fanconi anemia.Research square · 2023Article
- Personalized recurrence risk assessment following the birth of a child with a pathogenic de novo mutation.Nature communications · 2023Article
- The impact of paternal age on new mutations and disease in the next generation.Fertility and sterility · 2022Review
- Genetic analysis of 55 cases with fetal skeletal dysplasia.Orphanet journal of rare diseases · 2022Article
- High-level gonosomal mosaicism for a pathogenic non-coding CNV deletion of the lung-specific FOXF1 enhancer in an unaffected mother of an infant with ACDMPV.Molecular genetics & genomic medicine · 2022Article
- The False Dawn of Polygenic Risk Scores for Human Disease Prediction.Journal of personalized medicine · 2022Article
- Non-Invasive Detection of a De Novo Frameshift Variant ofJournal of clinical medicine · 2022Article
- Genome-wide DNA methylation profiling confirms a case of low-level mosaic Kabuki syndrome 1.American journal of medical genetics. Part A · 2022Article
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21 authors.
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Abstract
backgroundAlthough mosaic variation has been known to cause disease for decades, high-throughput sequencing technologies with the analytical sensitivity to consistently detect variants at reduced allelic fractions have only recently emerged as routine clinical diagnostic tests. To date, few systematic analyses of mosaic variants detected by diagnostic exome sequencing for diverse clinical indications have been performed.
methodsTo investigate the frequency, type, allelic fraction, and phenotypic consequences of clinically relevant somatic mosaic single nucleotide variants (SNVs) and characteristics of the corresponding genes, we retrospectively queried reported mosaic variants from a cohort of ~ 12,000 samples submitted for clinical exome sequencing (ES) at Baylor Genetics.
resultsWe found 120 mosaic variants involving 107 genes, including 80 mosaic SNVs in proband samples and 40 in parental/grandparental samples. Average mosaic alternate allele fraction (AAF) detected in autosomes and in X-linked disease genes in females was 18.2% compared with 34.8% in X-linked disease genes in males. Of these mosaic variants, 74 variants (61.7%) were classified as pathogenic or likely pathogenic and 46 (38.3%) as variants of uncertain significance. Mosaic variants occurred in disease genes associated with autosomal dominant (AD) or AD/autosomal recessive (AR) (67/120, 55.8%), X-linked (33/120, 27.5%), AD/somatic (10/120, 8.3%), and AR (8/120, 6.7%) inheritance. Of note, 1.7% (2/120) of variants were found in genes in which only somatic events have been described. Nine genes had recurrent mosaic events in unrelated individuals which accounted for 18.3% (22/120) of all detected mosaic variants in this study. The proband group was enriched for mosaicism affecting Ras signaling pathway genes.
conclusionsIn sum, an estimated 1.5% of all molecular diagnoses made in this cohort could be attributed to a mosaic variant detected in the proband, while parental mosaicism was identified in 0.3% of families analyzed. As ES design favors breadth over depth of coverage, this estimate of the prevalence of mosaic variants likely represents an underestimate of the total number of clinically relevant mosaic variants in our cohort.
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