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Leuk Lymphoma. 2019 Apr;60(4):1053-1061. doi: 10.1080/10428194.2018.1516039. Epub 2019 Feb 4.

Monozygotic twins with shared de novo GATA2 mutation but dissimilar phenotypes due to differential promoter methylation.

Author information

1
a Department of Laboratory Medicine , Seoul National University College of Medicine , Seoul , Republic of Korea.
2
b Division of Clinical Bioinformatics Biomedical Research Institute , Seoul National University Hospital , Seoul , Republic of Korea.
3
c Cancer Research Institute, Seoul National University College of Medicine , Seoul , Republic of Korea.
4
d Interdisciplinary program of Bioengineering , Seoul National University , Seoul , Republic of Korea.
5
e Department of Internal Medicine , Seoul National University College of Medicine , Seoul , Republic of Korea.
6
f Department of Laboratory Medicine , Korea Cancer Center Hospital , Seoul , Republic of Korea.

Abstract

A revised WHO classification of hematopoietic neoplasm introduced the new category 'Myeloid Neoplasms with Germline Predisposition', reflecting the growing importance of genetic testing for myeloid neoplasms. Here, we investigated monozygotic twins with the same de novo mutation in GATA2 but different phenotypes. The patient suffering a bleeding tendency was diagnosed with myelodysplastic syndrome (MDS), and her monozygotic twin showed dysmegakaryopoietic features in the bone marrow. Targeted sequencing revealed the same germline mutation in GATA2, c.1192C > T, in both sisters and different somatic mutations in 14 genes between the sisters. The GATA2 mutation was absent in both parents, and their hemograms were normal. The methylation profile of the GATA2 promoter region was different between the twins, showing denser promoter methylation in the patient, correlated with MDS. Thus, we concluded that the twins had acquired a de novo GATA2 mutation but showed different phenotypes, possibly due to the critical role of epigenetic changes.

KEYWORDS:

mutation; Familiar myelodysplastic syndrome/acute myeloid leukemia (MDS/AML); de novo mutation; monozygotic twin and DNA methylation

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