A Novel GATA-1 Mutation in a Neonate with Transient Abnormal Myelopoiesis without Down Syndrome

Haiying Chen, Johannes Wolff, Michael Chicka, Janet Cowan, Monika Pilichowska


Transient abnormal myelopoiesis (TAM) is a rare disorder usually diagnosed in newborns with Down syndrome, less frequently in mosaic trisomy 21 and only sporadically in phenotypically normal infants. In addition to the association with trisomy 21, TAM is also associated with mutations in the GATA-1 gene. We report a case of TAM with a novel mutation in the GATA-1 gene. A newborn boy was found to have leukocytosis (52.9 x 109/l) with 50% myeloid blast forms. Fluorescence in situ hybridization (FISH) on peripheral blood showed trisomy 21 limited to the blast forms. Further cytogenetic studies revealed that he did not have constitutional trisomy 21 or mosaic trisomy 21. Sequencing studies performed on DNA isolated from a peripheral blood sample containing blast forms showed a frameshift mutation in the GATA-1 gene (c.148_149dup CC) implying premature termination. A diagnosis of transient myeloproliferative disorder spectrum was made. The patient was treated with a short course of cytarabine with resolution of leukocytosis and a blast count of less than 0.5% at one month of age. Follow-up at 2 years after diagnosis showed normal peripheral blood counts and sustained molecular remission with normal karyotype. 


myeloproliferative disorder, Down syndrome, GATA-1 gene

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