Double somatic mosaicism in Cornelia de Lange syndrome

Am J Med Genet A. 2024 May;194(5):e63512. doi: 10.1002/ajmg.a.63512. Epub 2023 Dec 22.

Abstract

Post-zygotic mosaicism is a well-known biological phenomenon characterized by the presence of genetically distinct lineages of cells in the same individual due to post-zygotic de novo mutational events. It has been identified in about 13% of Cornelia de Lange (CdLS) syndrome patients with a molecular diagnosis, an unusual high frequency. Here, we report the case of a patient affected by classic CdLS harboring post-zygotic mosaicism for two different likely pathogenic variants at the same nucleotide position in NIPBL. Double somatic mosaicism has never been reported in CdLS and only rarely recognized in human diseases. Possible pathogenetic mechanisms are discussed.

Keywords: Cornelia de Lange syndrome; NIPBL; WES; cohesinopathies; double mosaicism; post‐zygotic mosaicism.

Publication types

  • Case Reports

MeSH terms

  • Cell Cycle Proteins / genetics
  • De Lange Syndrome* / diagnosis
  • De Lange Syndrome* / genetics
  • Humans
  • Mosaicism
  • Phenotype

Substances

  • Cell Cycle Proteins
  • NIPBL protein, human