GSE128718 Genetic disarray follows mutant KLF1-E325K expression in a congenital dyserythropoietic anemia patient

Contributors : James J Bieker ; Antanas PlanutisSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensCongenital dyserythropoietic anemia (CDA) type IV is caused by a heterozygous mutation, Glu325Lys (E325K), in the KLF1 transcription factor. A molecular understanding of this disease is absent, partly due to its rarity. We expanded erythroid cells from a patient ’s peripheral blood and analyzed its global expression pattern. We find that a large number of erythroid pathways are disrupted, particularly those related to membrane transport, globin regulation, and iron utilization. The altered genetics lead to significant deficits in differentiation. Glu325 i s within the KLF1 zinc finger domain at an amino acid critical for site specific DNA binding. The change to Lys is predicted to significantly alter the target site recognition sequence, both by subverting normal recognition and by enabling interaction with novel sites. Consistent with this, we find high level ectopic expression of genes not normally present in the red cell. These altered properties explain the patients’ clinical and phenotypic features and elucidate the dominant character of the mutation.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
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