Detection of the Hb Hoshida (HBB: C. 130 G > C) Variant in the Indian Population.

Abstract

Hemoglobinopathies, including thalassemias and structural hemoglobin variants, are among the most common monogenic disorders worldwide. In genetically heterogeneous populations such as India, screening programs occasionally detect rare hemoglobin variants that may mimic common abnormalities, leading to diagnostic uncertainty. During prenatal screening of an at-risk couple, we identified a rare β-globin gene variant, Hb Hoshida (HBB: c.130G > C), which results in a glutamic acid-to-glutamine substitution at codon 43 of the β-globin chain-reported here for the first time in India. The proband, a 23-year-old pregnant woman, was initially diagnosed as an HbE carrier by an external laboratory using high-performance liquid chromatography (HPLC), which showed a prominent peak in the HbA₂ window. Her husband was a carrier of β-thalassemia (HBB: c.92+5G>C).

Re-evaluation at our center showed an unusually high HbA₂-window peak (47.1%) with normal red cell indices, raising suspicion of a rare structural variant. Subsequent Sanger sequencing identified heterozygous Hb-Hoshida, and family studies confirmed it was paternally inherited.

Prenatal diagnosis by chorionic villus sampling revealed compound heterozygosity for Hb-Hoshida and β-thalassemia in the fetus. After genetic counseling about the uncertain clinical implications of this previously unreported genotype, the couple elected to terminate the pregnancy. In a subsequent pregnancy, prenatal testing showed that the fetus had not inherited either parental mutation, and the pregnancy progressed normally.

The identification of this rare variant emphasizes the need for cautious interpretation of hemoglobinopathy screening results in genetically heterogeneous populations and has important implications for genetic counseling and prenatal management.