A rare PALB2 germline variant causing G2/M cell cycle arrest is associated with isolated myelosarcoma in infancy

Research output: Contribution to journalResearch articleContributedpeer-review



BACKGROUND: Isolated myelosarcoma of infancy is a rare presentation of acute myelogenous leukaemia (AML). Because of its rarity and early onset in infancy underlying genetic predisposition is potentially relevant in disease initiation.

METHODS AND RESULTS: We report an oncologic emergency in an infant with thoracic and intraspinal aleukaemic myeloid sarcoma causing acute myelon compression and lower leg palsy. Whole-exome sequencing of the patient's germline DNA identified a rare PALB2 (OMIM 610355) variant (p.A1079S), which is located in a domain critical for the gene's proper function within the homology-directed repair pathway. In line with potential DNA damage repair defects mediated by the PALB2 deregulation, the patient's fibroblasts showed increased sensitivity towards radiation and DNA intercalating agents.

CONCLUSION: Therefore, we suggest PALB2 p.A1079S as a pathogenic variant potentially contributing to the here observed patient phenotype.


Original languageEnglish
Pages (from-to)e1746
JournalMolecular genetics & genomic medicine
Issue number9
Publication statusPublished - Aug 2021

External IDs

PubMedCentral PMC8457705
Scopus 85112263034
ORCID /0000-0002-3666-7128/work/147143664



  • Cells, Cultured, Fanconi Anemia Complementation Group N Protein/genetics, Fibroblasts/metabolism, G2 Phase Cell Cycle Checkpoints, Germ-Line Mutation, Humans, Infant, Male, Sarcoma, Myeloid/genetics, Spinal Neoplasms/genetics