Hb Lepore in the Indian population

Area of Science:

• Hematology
• Genetics
• Molecular Biology

Background:

• Beta-thalassemia is a group of inherited blood disorders characterized by reduced or absent beta-globin synthesis.
• Hb Lepore is a rare hemoglobin variant resulting from a fusion of delta and beta globin genes, often associated with beta-thalassemia phenotypes.

Purpose of the Study:

• To investigate the spectrum of beta-thalassemia mutations in patients with thalassemia major and intermedia.
• To identify and characterize Hb Lepore mutations within this patient cohort.
• To assess the diagnostic challenges associated with Hb Lepore heterozygosity.

Main Methods:

• Analysis of beta-thalassemia mutations in 230 patients with thalassemia major and 90 with thalassemia intermedia.
• Identification of Hb Lepore mutations using molecular techniques.
• Evaluation of cation exchange high-performance liquid chromatography for hemoglobin separation.

Main Results:

• Four patients (2 homozygous, 2 compound heterozygous) were found to have mutations producing Hb Lepore.
• Six delta beta fusion genes were identified, five producing Hb Lepore-Hollandia and one Hb Lepore-Washington-Boston.
• Cation exchange high-performance liquid chromatography showed poor separation between Hb Lepore and Hb A2 in heterozygous states, suggesting potential misdiagnosis.

Conclusions:

• Hb Lepore mutations can contribute to both thalassemia major and intermedia phenotypes.
• The diagnostic methodology for Hb Lepore heterozygotes requires careful consideration due to chromatographic limitations.
• Accurate identification of Hb Lepore is crucial for genetic counseling and patient management in beta-thalassemia.