Identification of a Rare β-Globin Chain Hemoglobin Variant: HBB: C.24G > C (Glu7Asp)

We report the identification and characterization of a rare hemoglobin variant resulting from a mutation in the β-globin chain gene. The case involved a 36-year-old Han Chinese woman who was initially identified through a routine blood test that showed red blood cell microcytosis and hypochromia. Subsequent hemoglobin analysis using capillary electrophoresis revealed an unusual chromatographic pattern, characterized by a significant shoulder peak adjacent to the normal hemoglobin A (HbA), alongside the expected HbA and HbA2 peaks. To determine the genetic basis of this abnormality, HBB gene sequencing was performed. This analysis identified a heterozygous missense mutation, c.24G > C, located in exon 1. This mutation results in a GAG > GAC codon change, corresponding to a substitution of glutamic acid for aspartic acid at position 7 of the β-globin chain (Glu7Asp). This study represents the first detailed clinical and molecular description of this particular variant. The variant has been submitted to the IthaGenes global hemoglobin variant database with the submission ID 4156. In silico analysis using the PolyPhen-2 algorithm predicted this variant as 'probably damaging', with a score of 0.998. This report enriches the clinical and hematological information available for this HBB gene variant. Its accurate identification is crucial to prevent misdiagnosis and to ensure appropriate and reliable genetic counseling and prenatal diagnosis for affected individuals and their families.