Dr. Mayka Sánchez attended the LXV National Congress of SEHH and XXXIX National Congress of SETH to discuss her new paper, which was carried out jointly with her research team from the International University of Catalonia (UIC).

All reported cases of CDA III present with a core phenotype consisting of a variable degree of macrocytic anemia, signs of intravascular hemolysis, and giant multinucleated erythroblasts in the bone marrow.

Moreover, additional symptoms such as multiple myeloma, monoclonal gammopathy, angioid streaks, hemosiderinuria, hepatosplenomegaly, iron overload, or cirrhosis have been described in some patients with CDA III. Using next-generation sequencing (NGS) in combination with ex vivo erythroid differentiation, we identified two pathogenic missense mutations in the RACGAP1 gene in three unrelated families affected with the recessive form of CDA III.

The new paper can be found in NCBI: Mutations in the RACGAP1 gene cause autosomal recessive congenital dyserythropoietic anemia type III.

Congenital dyserythropoietic anemia type III (CDA III) is one of the rarest forms of CDA. The autosomal dominant form of CDA III is known to be due to monoallelic mutations in the KIF23 gene; so far, two of these mutations have been described in a total of three families.

KIF23 encodes the mitotic kinesin-like protein MKLP1, which dimerizes and combines with a homodimer of the RACGAP1 protein (Rac GTPase-activating protein 1) to form the centralspindlin complex that regulates Rho GTPase activity and is necessary for cytokinesis. Sporadic cases with CDA III pathology have been reported, suggesting a different genetic alteration.