Genetic Heterogeneity of β-thalassemia Variants in Affected Filipinos.

Abstract

Background: β-thalassemia, a hereditary blood disorder, is characterized by the reduction or absence of β-globin chain synthesis, with disease severity depending on population-specific HBB variants. This is the first report to present the molecular profile of Filipino β-thalassemia patients.

Methods: Deletion analysis, β-globin StripAssay analysis, and HBB gene sequencing were performed in 237 patients with β-thalassemia.

Results: Twenty-one (21) previously published β-thalassemia variants - ten (10) pathogenic point mutations [c.79G>A (HbE) (48.52%), c.92+2T>C (1.47%), c.52A>T (0.84%), c.92+5G>C (0.63%), c.-50A>C (cap+1) (0.42%), c.79G>T (0.21%), c.59A>G (Malay) (0.21%), c.47G>A (0.21%), c.20A>T (HbS) (0.21%), and c.2T>G (initiation codon) (0.21%)]; five (5) pathogenic deletions [HBB Filipino deletion (23.42%), c.203_204delTG (5.49%), c.126_129delCTTT (codon 41/42) (1.68%), c.155delC (0.63%), and c.110delC (0.21%)]; two (2) conflicting patterns of pathogenicity [c.27dup (0.42%) and c.170G>A Hb J-Bangkok (0.21%)]; and four (4) polymorphisms [c.9T>C (codon 2) (40.93%), c.315+16G>C (36.92%), c.316-185C>T (25.74%), and c.-92C>G (0.21%) - were identified.

Conclusion: The genetic heterogeneity of β-thalassemia in affected Filipinos emphasizes the value of mutation-based confirmation for diagnosis, carrier screening, genetic counseling, disease management, and formulation of nationwide health policies.