GATA1 - Disease Linkage

Disease Linkage

Mutations in exon 2 of the GATA1 gene are present in almost all cases of Down syndrome (DS)-associated acute megakaryoblastic leukemia (AMKL). While AMKL is typically associated with the (1;22) translocation and expression of a mutant fusion protein, the genetic alterations that promote individuals with DS-AMKL are related to the GATA1 mutations, and the formation of a truncated transcription factor (GATA1s).

The same mutations in exon 2 of GATA1 present in almost all Down Syndrome-associated transient myeloproliferative disorder (TMD) or transient leukemia (TL), a precursor condition that evolves into AMKL in 30% of patients, that as many as 10% of Down Syndrome children may develop. The incidence for the GATA1 mutation in about 4% of Down Syndrome patients, but less than 10% of those with the mutation developed AMKL. This mutation is present in the fetus, suggesting an early role in leukemogenesis. In addition to screening for TL, a GATA1 mutation at birth might serve as a bio-marker for an increased risk of DS-related AMKL.

Increased levels of GATA1 expression have been found in individuals with major depressive disorder. Expression of GATA1 in the prefrontal cortex results in a decrease of the expression of synapse-related genes, a loss of dendritic spines and dendrites, and can produce depressive behavior in rat models of depression.