Hereditary Persistence of Fetal Hemoglobin (HPFH): Detection of Unknow ^A γ-Globin Promoter Mutation at the C2H2 Zinc Finger Transcription Factors Binding Sites

A 31-year-old pregnant African woman presents to our unit following hemoglobin-HPLC analysis, which reveals a slightly elevated HbF fraction (4.2%). Molecular analysis of the α and β-globin genes did not detect any mutations. To further investigate her persistent fetal hemoglobin (HPFH), we performed Sanger sequencing of the γ-globin promoter. This analysis uncovered two unknow point mutations: <i>HBG1</i>: c.-305 A > G and <i>HBG2</i>: c.-309 A > G. Notably, the mutation in the ^Aγ-globin promoter lies within the AGGAA binding site of the C2H2 zinc finger transcription factor IZKF1. This mutation may account for the patient's HPFH and highlights the importance of analyzing all promoter binding sites in genome editing-based therapies for β-thalassemia.