title: A novel mutation in the GATA1 gene associated with acute megakaryoblastic leukemia in a Korean Down syndrome patient.
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.
authors.affiliation: Department of Laboratory Medicine, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: In-Suk
authors.initials: IS
authors.lastname: Kim
authors.forename: Eun Sil
authors.initials: ES
authors.lastname: Park
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Lim
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Chi
mesh_terms: D001483:Base Sequence; D002675:Child, Preschool; D002891:Chromosomes, Human, Pair 21; D004314:Down Syndrome / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D050982:GATA1 Transcription Factor / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D007723:Korea; D007947:Leukemia, Megakaryoblastic, Acute / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D014314:Trisomy
chemical_list: D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human