Parental mosaicism for apparent de novo genetic variants: Scope, detection, and counseling challenges

Roni Zemet, Ignatia B. Van den Veyver*, Paweł Stankiewicz*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


The disease burden of de novo mutations (DNMs) has been evidenced only recently when the common application of next-generation sequencing technologies enabled their reliable and affordable detection through family-based clinical exome or genome sequencing. Implementation of exome sequencing into prenatal diagnostics revealed that up to 63% of pathogenic or likely pathogenic variants associated with fetal structural anomalies are apparently de novo, primarily for autosomal dominant disorders. Apparent DNMs have been considered to primarily occur as germline or zygotic events, with consequently negligible recurrence risks. However, there is now evidence that a considerable proportion of them are in fact inherited from a parent mosaic for the variant. Here, we review the burden of DNMs in prenatal diagnostics and the influence of parental mosaicism on the interpretation of apparent DNMs and discuss the challenges with detecting and quantifying parental mosaicism and its effect on recurrence risk. We also describe new bioinformatic and technological tools developed to assess mosaicism and discuss how they improve the accuracy of reproductive risk counseling when parental mosaicism is detected.

Original languageEnglish
Pages (from-to)811-821
Number of pages11
JournalPrenatal Diagnosis
Issue number7
StatePublished - Jun 2022
Externally publishedYes


FundersFunder number
National Institutes of HealthT32 GM07526‐44
National Institute of General Medical SciencesT32GM007526
National Institute of Child Health and Human Development
Baylor College of MedicineR01HD087292
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentR01HD055651, P50HD103555


    • De novo mutation
    • mosaicism
    • prenatal diagnosis
    • recurrence risk
    • variants


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