Open AccessA rare PALB2 germline variant causing G2/M cell cycle arrest is associated with isolated myelosarcoma in infancy
Author(s) -
Beer Angelina,
Beck Ricardo,
Schedel Anne,
Bonin Malte,
Meinel Jörn,
Friedrich Ulrike Anne,
Menzel Maria,
Suttorp Meinolf,
Brenner Sebastian,
Fitze Guido,
Lange Björn,
Knöfler Ralf,
Hauer Julia,
Auer Franziska
Publication year - 2021
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1746
Subject(s) - palb2 , germline , fanca , medicine , cancer research , exome sequencing , genetic predisposition , germline mutation , dna repair , genetics , biology , phenotype , bioinformatics , gene , mutation , fanconi anemia
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.