Duncan NRI Faculty and Staff Publications
Language
English
Publication Date
6-1-2022
Journal
Prenatal Diagnosis
DOI
10.1002/pd.6144
PMID
35394072
PMCID
PMC9995893
PubMedCentral® Posted Date
6-1-2023
PubMedCentral® Full Text Version
Author MSS
Abstract
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.
Keywords
Counseling, Female, Humans, Mosaicism, Mutation, Parents, Pregnancy, Pregnancy Trimester, First, Ultrasonography, Prenatal
Published Open-Access
yes
Recommended Citation
Roni Zemet, Ignatia B Van den Veyver, and Paweł Stankiewicz, "Parental Mosaicism for Apparent De Novo Genetic Variants: Scope, Detection, and Counseling Challenges" (2022). Duncan NRI Faculty and Staff Publications. 185.
https://digitalcommons.library.tmc.edu/duncar_nri_pub/185
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Genetic Phenomena Commons, Medical Genetics Commons, Neurology Commons, Neurosciences Commons