KLF1 gene

A variant (also called a mutation) in the KLF1 gene has been identified in people with congenital dyserythropoietic anemia (CDA) type IV. This condition is characterized by a shortage of red blood cells that is caused by abnormal red blood cell formation (dyserythropoietic anemia). In people with CDA type IV, immature red blood cells are abnormal and cannot develop into functional, mature cells. This often leads to weakness, an enlarged liver and spleen (hepatosplenomegaly), the buildup of too much iron (iron overload), and short stature in people with CDA type IV. The anemia in CDA type IV often begins prenatally or soon after birth, and it is typically severe.

The KLF1 gene variant leads to a change in a single protein building block (amino acid) in the protein. The KLF1 gene variant that causes CDA type IV reduces the function of the protein and disrupts its regulation of multiple genes that are involved in the normal development of red blood cells. People with CDA type IV tend to produce higher than normal levels of fetal hemoglobin throughout their lives. In people with CDA type IV, immature red blood cells called erythroblasts are unusually shaped and may have more than one nucleus. These defective erythroblasts cannot develop into functional, mature red blood cells. The resulting shortage of healthy red blood cells leads to the characteristic signs and symptoms of anemia and the other features of CDA type IV.