Prevalence of germlineGATA2andSAMD9/9Lvariants in paediatric haematological disorders with monosomy 7

Abstract

Monosomy 7 (-7) occurs in various types of paediatric myeloid disorders and has a poor prognosis. Recent studies have demonstrated that patients with germline gain-of-functionSAMD9/9Lvariants and loss-of-functionGATA2variants are prone to developing myelodysplastic syndrome (MDS) associated with -7. However, the prevalence of the genetic variants among paediatric haematologic disorders with -7 is unknown. The present study screened germline variants ofGATA2andSAMD9/9Lin 25 patients with various types of paediatric haematological disorders associated with -7. The diagnoses of the 25 patients included MDS (n = 10), acute myeloid leukaemia (AML) and myeloid sarcomas (n = 9), juvenile myelomonocytic leukaemia (n = 3) and other disorders (n = 3). Seven patients with a germline pathogenicGATA2variant were found. ForSAMD9/9Lscreening, next-generation sequencing was used to detect low-abundance variants and found four novel germline variants. Functional analysis revealed that three out of the four variants showed growth-restricting capacityin vitroand thus, were judged to be pathogenic. Cases withGATA2mutation tended to be older, compared to those withSAMD9/9Lmutations. In conclusion,GATA2andSAMD9/9Lwere sequenced in 25 patients with paediatric haematologic disorders associated with -7, and 40% of them were found to have some pathogenic germline variants in the three genes.