Utility of Molecular Sequencing and Hematologic Parameters for Diagnosis of α-Thalassemia: A Perspective of the National Reference Laboratory

Document Type

Article

Publication Date

11-1-2025

Abstract

α-Thalassemia is a prevalent genetic disorder, and recent global migration has increased the need for effective screening and diagnosis, even in historically low-prevalence regions. Accurate diagnosis of symptomatic individuals and carriers is essential for appropriate management. This multi-year retrospective study presents 776 cases correlating CBC parameters, hemoglobin fractionation, α-globin gene deletion/duplication analysis, and complete α-globin sequencing. Among these cases, 174 (22%) had abnormal Hb fractionation patterns by HPLC, and 602 (78%) had normal pattern. By deletion/duplication analysis, 576 (74%) had an intact α-globin gene cluster, while deletions were detected in 24% (188/776) of cases; 103 (13%) with one-gene, 82 (11%) two-gene, 3 (0.3%) with three-gene deletions, and 12 (1.5%) had α- gene triplication. Sequencing identified variant hemoglobin in 198 (26%) samples, including 163 α-globin variants, the remaining 36 variants were either β or delta globin variants. Notably, 28 α-globin variants were undetectable by HPLC/CE, 18 of which were non-deletional or 'thalassemic' variants. A total of 72 (9.3%) samples were found to have combined α-globin gene deletion and an α-globin variant. CBC parameters showed no significant differences between normal individuals and those with one or more α-gene deletions or non-deletional α-globin variants. EMQN thresholds demonstrated 81% sensitivity and 25% specificity for detecting deletional α-thalassemia. Our findings highlight the utility of molecular analysis for carrier detection and the necessity of α-globin full gene sequencing in cases with unexplained clinical phenotypes.

Link to Full Text

Share

COinS