Autosomal Dominant Erythrocytosis Caused by Non-Renal Erythropoietin (EPO) Due to EPO c.-136 G>A Germline Mutation.

ABSTRACT: We previously reported a five-generation kindred with autosomal dominant erythrocytosis associated with a novel germline promoter variant in the erythropoietin (EPO) gene (EPO c.-136 G>A). This mutation creates a new hypoxia response element (HRE) consensus sequence on the reverse strand suggesting a gain of function mutation. CRISPR/Cas9-edited Hep3B cells harboring the c.-136 G>A variant had increased EPO mRNA and protein expression under both normoxic and hypoxic conditions compared to wild-type cells; functional assays confirmed the activity of the c.-136 G>A variant-induced EPO. Isoelectric focusing analyses of patient urine and plasma showed a more basic EPO isoform pattern, consistent with the reduced sulfated N-glycan contribution, suggesting decreased renal and increased non-renal

SUBMITTER: Lanikova L 

PROVIDER: S-EPMC12994116 | biostudies-literature | 2026 Apr

REPOSITORIES: biostudies-literature