High penetrance of myeloid neoplasia with diverse clinical and cytogenetic features in three siblings with a familial GATA2 deficiency
AuthorsEllingford, J. M.
Will, A. M.
Black, G. C.
Wynn, R. F
AffiliationManchester Centre for Genomic Medicine, North West Genomic Laboratory Hub, Manchester NHS Foundation Trust, Manchester, UK;
MetadataShow full item record
AbstractPathogenic germ-line variants in GATA2 (GATA2-deficiency) can cause childhood myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML), and can be associated with distinct clinical syndromic features. However, penetrance and genotype-phenotype correlations are incompletely understood. Here we report on the clinically diverse features of three siblings affected by GATA2c.1021_1031del over an 18-year period, all initially presenting in childhood and adolescence with MDS and AML with monosomy 7 (-7), and one also with trisomy 8 (+8). The siblings inherited a GATA2c.1021_1031del from their father who remains asymptomatic in his sixth decade. The two younger sisters are well after unrelated haematopoietic stem cell transplantation (HSCT), while the first boy died of severe chronic lung disease after sibling HSCT from his youngest sister, who subsequently also developed GATA2-deficiency associated MDS. This family illustrates high penetrance with variable genotype/phenotype correlation within one generation with GATA2-deficiency. We surmise that the lung disease post sibling HSCT was also caused by the GATA2-deficiency. The experience with this family underlines the necessity for GATA2 analysis in all apparently sporadic childhood and teenage MDS and AML with -7 also in the absence of a family history or other clinical features, and rigorous genetic testing in siblings. Moreover, our findings support the arguments for pre-emptive HSCT in variant-carrying siblings.
CitationEllingford JM, Telford N, Urquhart J, Will AM, Bonney D, Adams B, et al. High penetrance of myeloid neoplasia with diverse clinical and cytogenetic features in three siblings with a familial GATA2 deficiency. Cancer Genetics. 2021 Aug;256–257:77–80.
- Somatic mutations in children with <i>GATA2</i>-associated myelodysplastic syndrome who lack other features of GATA2 deficiency.
- Authors: Fisher KE, Hsu AP, Williams CL, Sayeed H, Merritt BY, Elghetany MT, Holland SM, Bertuch AA, Gramatges MM
- Issue date: 2017 Feb 28
- Donor-derived myelodysplastic syndrome after allogeneic stem cell transplantation in a family with germline GATA2 mutation.
- Authors: Sakata N, Okano M, Masako R, Tanaka A, Yamashita Y, Karasuno T, Imadome KI, Okada M, Sugimoto K
- Issue date: 2021 Feb
- Heritable GATA2 mutations associated with familial AML-MDS: a case report and review of literature.
- Authors: Gao J, Gentzler RD, Timms AE, Horwitz MS, Frankfurt O, Altman JK, Peterson LC
- Issue date: 2014 Apr 22
- Heterogeneity of GATA2-related myeloid neoplasms.
- Authors: Hirabayashi S, Wlodarski MW, Kozyra E, Niemeyer CM
- Issue date: 2017 Aug
- Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents.
- Authors: Wlodarski MW, Hirabayashi S, Pastor V, Starý J, Hasle H, Masetti R, Dworzak M, Schmugge M, van den Heuvel-Eibrink M, Ussowicz M, De Moerloose B, Catala A, Smith OP, Sedlacek P, Lankester AC, Zecca M, Bordon V, Matthes-Martin S, Abrahamsson J, Kühl JS, Sykora KW, Albert MH, Przychodzien B, Maciejewski JP, Schwarz S, Göhring G, Schlegelberger B, Cseh A, Noellke P, Yoshimi A, Locatelli F, Baumann I, Strahm B, Niemeyer CM, EWOG-MDS.
- Issue date: 2016 Mar 17