Parental somatic mosaicism for CNV deletions - A need for more sensitive and precise detection methods in clinical diagnostics settings

Genomics. 2020 Sep;112(5):2937-2941. doi: 10.1016/j.ygeno.2020.05.003. Epub 2020 May 6.


To further assess the scale and level of parental somatic mosaicism, we queried the CMA database at Baylor Genetics. We selected 50 unrelated families where clinically relevant apparent de novo CNV-deletions were found in the affected probands. Parental blood samples screening using deletion junction-specific PCR revealed four parents with somatic mosaicism. Droplet digital PCR (ddPCR), qPCR, and amplicon-based next-generation sequencing (NGS) were applied to validate these findings. Using ddPCR levels of mosaicism ranged from undetectable to 18.5%. Amplicon-based NGS and qPCR for the father with undetectable mosaicism was able to detect mosaicism at 0.39%. In one mother, ddPCR analysis revealed 15.6%, 10.6%, 8.2%, and undetectable levels of mosaicism in her blood, buccal cells, saliva, and urine samples, respectively. Our data suggest that more sensitive and precise methods, e.g. CNV junction-specific LR-PCR, ddPCR, or qPCR may allow for a more refined assessment of the potential disease recurrence risk for an identified variant.

Keywords: Clinical diagnostic testing; Copy-number variant (CNV); Mosaicism carrier; Parental somatic mosaicism; Recurrence risk.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Clinical Laboratory Techniques
  • DNA Copy Number Variations*
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Inheritance Patterns
  • Male
  • Mosaicism*
  • Polymerase Chain Reaction*
  • Sequence Analysis, DNA