Prospective screening for δ-hemoglobinopathies associated with decreased hemoglobin A 2 levels or hemoglobin A 2 variants: A single center experience.

Background: δ-hemoglobinopathies may lead to misdiagnosis of several thalassemia syndromes especially β-thalassaemia carrier, it is important to evaluate the δ-globin gene defects in areas with high prevalence of globin gene disorders. We describe a prospective screening for δ-hemoglobinopathies in a routine setting in Thailand.
Methods: Study was done on a cohort of 8,471 subjects referred for thalassemia screening, 317 (3.7%) were suspected of having δ-globin gene defects due to reduced hemoglobin (Hb) A ₂ levels and/or appearance of Hb A ₂ -variants on hemoglobin analysis. Hematologic and DNA analysis by PCR and related assays were carried out.
Results: DNA analysis of δ-globin gene identified seven different δ-globin mutations in 24 of 317 subjects (7.6%). Both known mutations; δ ^-77(T>C) (n = 3), δ ^-68(C>T) (n = 1), δ ^-44(G>A) (n = 8), Hb A ₂ -Melbourne (n = 5), δ ^{IVSII-897(A>C)} (n = 5), and Hb A ₂ -Troodos (n = 1) and a novel mutation; the Hb A ₂ -Roi-Et (n = 1) were identified. This Hb A ₂ -Roi-Et, results from a double mutations in-cis, δ ^{CD82(AAG>AAT)} and δ ^{CD133(GTG>ATG)} , was interestingly found in combination with an in trans, 12.6 kb deletional δβ ⁰ -thalassemia in an adult Thai woman who had no Hb A ₂ and elevated Hb F. A multiplex-allele-specific PCR was developed to detect these novel δ-globin gene defects.
Conclusions: The result confirms a diverse heterogeneity of δ-hemoglobinopathies in Thailand which should prove useful in a prevention and control program of thalassemia in the region.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)