A Novel Mutation in the GATA1 Gene Associated with Acute Megakaryoblastic Leukemia in a Korean Down Syndrome Patient.
10.3346/jkms.2008.23.6.1105
- Author:
In Suk KIM
1
;
Eun Sil PARK
;
Jae Young LIM
;
Chang Seok KI
;
Hyun Sook CHI
Author Information
1. Department of Laboratory Medicine, Gyeongsang National University Hospital, Jinju, Korea.
- Publication Type:Case Report
- Keywords:
Leukemia, Megakaryoblastic, Acute;
Down Syndrome;
GATA1 Transcription Factor;
Korea
- MeSH:
Base Sequence;
Child, Preschool;
Chromosomes, Human, Pair 21;
Down Syndrome/complications/diagnosis/*genetics;
Female;
GATA1 Transcription Factor/*genetics;
Humans;
Karyotyping;
Korea;
Leukemia, Megakaryoblastic, Acute/diagnosis/etiology/*genetics;
*Mutation;
Phenotype;
Trisomy
- From:Journal of Korean Medical Science
2008;23(6):1105-1108
- CountryRepublic of Korea
- Language:English
-
Abstract:
Although acquired mutations in the GATA1 gene have been reported for Down syndrome-related acute megakaryoblastic leukemia (DS-AMKL) in Caucasians, this is the first report of a Korean Down syndrome patient with AMKL carrying a novel mutation of the GATA1 gene. A 3-yr-old Korean girl with Down syndrome was admitted to our hospital complaining of pallor and fever. The findings of a peripheral blood smear and bone marrow study were compatible with the presence of AMKL. A chromosome study showed 48,XX,-7,+21c,+21,+r[3]/47,XX,+21c[17]. Following GATA1 gene mutation analysis, a novel mutation, c.145dupG (p.Ala49GlyfsX18), was identified in the N-terminal activation domain of the GATA1 gene. This mutation caused a premature termination at codon 67 and expression of an abnormal GATA-1 protein with a defective N-terminal activation domain, and the absence of full-length GATA-1 protein. This case demonstrates that a leukemogenic mechanism for DS-AMKL is contributed by a unique collaboration between overexpressed genes from trisomy 21 and an acquired GATA1 mutation previously seen in Caucasians and now in a Korean patient.
