Identification of a Novel Compound Heterozygous SEC23B in a Chinese Child with Congenital Dyserythropoietic Anemia...

Congenital dyserythropoietic anemia type II (CDA II) is a rare hyporegenerative inherited anemia, resulting from a mutation in SEC23B. In the present case, our patient exhibited moderate anemia, jaundice, hepatosplenomegaly, tea-colored urine, hyperbilirubinemia, and iron overload. Whole exome sequencing revealed that the patient carried a compound heterozygous genotype in SEC23B consisting of a previously unreported missense variant c.181T > C (p.C61R) and a known pathogenic variant c.1832G > A (p.R611Q). Bone marrow aspirate demonstrated erythroid hyperplasia with abnormal erythroblast morphology. Bioinformatic analysis predicted the protein structures, indicating that p.C61R and p.R611Q mutations induce structural changes in their surrounding regions. SEC23B mRNA and protein levels in peripheral blood mononuclear cells (PBMCs) were significantly reduced compared with those in normal control cells, supporting their pathogenicity. Accordingly, a diagnosis of CDA II was considered. In this study, we identified a compound heterozygous SEC23B genotype in the patient and demonstrated that missense mutations of p.C61R and p.R611Q resulted in reduced levels of SEC23B mRNA and protein, suggesting the association of this genotype with CDA II.