Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Apr;39(4):962-966.
doi: 10.1038/s41375-025-02519-4. Epub 2025 Jan 31.

Multiple phenotypes and epigenetic profiles in a three-generation family history with GATA2 deficiency

Damia Romero-Moya #  1 , Joan Pera  2   3 , Oskar Marin-Bejar  2   4 , Eric Torralba-Sales  2 , Laura Murillo-Sanjuán  5 , Cristina Diaz-de-Heredia  5 , Julia Montoro  6 , Javier Rodríguez-Ubreva  7 , Alessandro Liquori  8   9 , José Cervera  8   9 , Marcin W Wlodarski  10 , Albert Català  3   11 , Alessandra Giorgetti #  12   13
Affiliations

Multiple phenotypes and epigenetic profiles in a three-generation family history with GATA2 deficiency

Damia Romero-Moya et al. Leukemia. 2025 Apr.
No abstract available

PubMed Disclaimer

Conflict of interest statement

Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All methods were performed in accordance with the relevant guidelines and regulations. This study was approved by institutional review boards at Bellvitge (PR097-20) and Sant Joan de Déu (PIC-141-20) Hospitals. All patients or their guardians signed informed consents for sample collection in accordance with the Declaration of Helsinki.

Figures

Fig. 1
Fig. 1. Characterization of a GATA2-mutant pedigree with variable disease manifestations.
A Genogram of the GATA2-mutated pedigree. Squares denote males and circles denote females. This three-generation GATA2 family presented four members with identical germline GATA2 mutations (p. Met388Thr; c.1163T>C) and variable clinical manifestations. B Principal Component Analysis (PCA) showing the distribution of GATA2 carriers (P#) and healthy donors (HD), based on DNA methylation profile of peripheral blood samples. C Number and percentage of hypomethylated and hypermethylated differentially methylated positions (DMPs) of each patient compared to the HD group. D) Heatmap of DMPs of peripheral blood. The hypermethylated DMP cluster in P3 and P4 samples is squared in red (Cluster A). The hypomethylated DMP cluster only in P4 samples is squared in blue (Cluster B). Scale β-values from -3 (blue/hypomethylated) to +3 (red/hypermethylated). Raw reads were processed using ShinyEpico (v1.14.0) package in R (v4.2.0). β-values are used to calculate the differences between groups. Δβ-value was considered significant when ≥0.225 and p-adj ≤ 0.05. P-value was calculated using the empirical Bayes moderated two-sided t-test. P-value is then adjusted using the Benjamini-Hochberg (FDR) method.
Fig. 2
Fig. 2. Epigenetic evolution highlights methylation changes in key hematopoietic genes.
A Venn diagram of hypermethylated and hypomethylated genes of P3 and P4 from promoter associated differentially methylated positions (DMPs) compared to gene list described in Marin-Bejar et al. [3]. Full list can be found in Table S2. B Left, list of selected genes of intersection between P3 and P4 (420 hypermethylated and 73 hypomethylated) from Fig. 2A. Right, list of selected genes of intersection between P3, P4 and Marin-Bejar et al. [3] (52 hypermethylated and 3 hypomethylated) from Fig. 2A. Scale of Δβ-values from −0.4 to 0.4 compared to healthy donors (HD). Underscore genes are mentioned in the manuscript. Gene in Bold are GATA2 targets. Full list can be found in Table S2. C Five stage-specific groups of hypermethylated (red) and hypomethylated (blue) genes from promoter associated DMPs across all P4 time points (P4.1, P4.2, and P4.3). The specific number of genes is indicated. Color range from 0 to 1000. D Left, list of selected genes that are in common across all P4 time points (704 hypermethylated and 311 hypomethylated) from Fig. 2C. Right, list of selected genes that are acquired during P4 disease evolution, P4.2 specific, P4.3 specific and P4.2 + P4.3 (1018 hypermethylated and 720 hypomethylated) from Fig. 2C. Scale of Δβ-values from −0.4 to 0.4 compared to HD. Underscore genes are mentioned in the manuscript.
See this image and copyright information in PMC

References

    1. Calvo KR, Hickstein DD. The spectrum of GATA2 deficiency syndrome. Blood. 2023;141:1524–32. - PMC - PubMed
    1. Wlodarski MW, Hirabayashi S, Pastor V, Stary J, Hasle H, Masetti R, et al. Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents. Blood. 2016;127:1387–97. - PubMed
    1. Marin-Bejar O, Romero-Moya D, Rodriguez-Ubreva J, Distefano M, Lessi F, Aretini P, et al. Epigenome profiling reveals aberrant DNA methylation signature in GATA2 deficiency. Haematologica. 2023;108:2551–7. - PMC - PubMed
    1. Oleaga-Quintas C, de Oliveira-Junior EB, Rosain J, Rapaport F, Deswarte C, Guerin A, et al. Inherited GATA2 deficiency Is dominant by haploinsufficiency and displays incomplete clinical penetrance. J Clin Immunol. 2021;41:639–57. - PMC - PubMed
    1. Fujiwara T, O’Geen H, Keles S, Blahnik K, Linnemann AK, Kang YA, et al. Discovering hematopoietic mechanisms through genome-wide analysis of GATA factor chromatin occupancy. Mol Cell. 2009;36:667–81. - PMC - PubMed