Masking of a β-Thalassemia Determinant by a Novel δ-Globin Gene Defect [Hb A₂-Saurashtra or δ100(G2)Pro→Ser; HBD: c.301C>T] in Cis

Abstract

The molecular basis of β-thalassemia (β-thal) syndromes have been well documented, while the spectrum of mutations causing δ-thalassemia (δ-thal) has not been well characterized. δ-Thalassemia has no clinical symptoms but its coinheritance with heterozygous β-thal may cause misdiagnosis, especially in countries with a high prevalence of β-thal where prevention programs have been implemented. The coinheritance of β- and δ-globin mutations in India is not common. This association may interfere with correct diagnosis and genetic counseling of β-thal in screening programs. Here we report two families showing borderline Hb A₂ levels belonging to the Koli Community, indigenous to the Saurashtra Province of Gujarat, India. They were referred to us for thalassemia molecular screening as they had children clinically presenting before 2 years of age and requiring regular blood transfusions. Interestingly, both families carried a novel δ-globin gene mutation at codon 100 (C>T) linked to a polyadenylation (polyA) site [AATAAA>A(–AATAA)] 5 bp deletional β-thal mutation, never before reported in the Indian population. This report highlights the importance of considering δ-globin gene analysis during β-thal screening to avoid false-negative results in the detection of at-risk couples. It also highlights how incomplete diagnosis of a borderline or normal Hb A₂ level may lead to the probable birth of a β-thal major (β-TM) child. This has important implications in prenatal diagnosis.

• β-Globin gene
• β-thalassemia (β-thal)
• borderline Hb A₂ level
• India