Clinical and Molecular Characterization of β^S and ^Gγ(^Aγδβ)⁰-Thalassemia in Eastern India

Abstract

Fetal hemoglobin (Hb F) is the most studied modifier of sickle cell disease. Coinheritance of high Hb F determinants such as δβ-thalassemia (δβ-thal) and hereditary persistence of fetal hemoglobin (HPFH) can contribute to raised Hb F concentration in these patients. One hundred and seventy-six cases of sickle cell disease with high Hb F were screened for the presence of the Asian Indian deletion-inversion ^Gγ(^Aγδβ)⁰-thal and HPFH-3 (Indian, 48.5 kb) disorders. Three cases from two unrelated families were found to have sickle cell disease and the (^Aγδβ)⁰-thal genotype. Three other members had heterozygous ^Gγ(^Aγδβ)⁰-thal. None had HPFH-3. Despite very high Hb F concentrations and linkage of the β^S gene to Asian haplotypes, the compound heterozygotes had severe clinical presentation, possibly because of heterocellular distribution of Hb F. In conclusion, these high Hb F determinants are not common causes of high Hb F in Indian sickle cell disease patients.

• ^Gγ(^Aγδβ)⁰-Thalassemia [^Gγ(^Aγδβ)⁰-thal]
• Hereditary persistence of fetal hemoglobin (HPFH)
• Sickle cell disease
• Hb F
• India