Molecular characteristics of α + -thalassemia (3.7 kb deletion) in Southeast Asia: Molecular subtypes, haplotypic heterogeneity, multiple founder effects and laboratory diagnostics.

Objective: The 3.7 kb deletion (-α ^3.7 ) is the most common form of α ⁺ -thalassemia found in multiple populations which can be classified into three subtypes. In order not to mis-identify it, the molecular information within each population is required. We have addressed this in northeast Thai and Laos populations.
Methods: Screening for α ⁺ -thalassemia was initially done on 1192 adult Thai subjects. In addition, 77 chromosomes of Thai newborns and 26 chromosomes of Laos with -α ^3.7 α ⁺ -thalassemia were also examined. All subjects were screened for -α ^3.7 α ⁺ -thalassemia and subtyped by PCR-RFLP assay. Exact deletion breakpoint of each -α ^3.7 subtype was determined by DNA sequencing. α-Globin gene haplotypes were determined.
Results: The proportions of -α ^3.7 subtypes found in 216 Thai -α ^3.7 chromosomes were 94.9% for -α ^3.7I , 4.2% for α ^3.7II and 0.9% for -α ^3.7III . All 26 Laos -α ^3.7 chromosomes were of -α ^3.7I variety. At least six α-globin gene haplotypes were associated with the -α ^3.7I α ⁺ -thalassemia.
Conclusion: All -α ^3.7 subtypes were observed among Southeast Asian population. Haplotype analysis indicated a multiple origin of this common disorder in the region. A multiplex PCR assay has been developed for simultaneous detection of all subtypes of -α ^3.7 α ⁺ -thalassemia as well as other α ⁺ -thalassemia found in the region including -α ^4.2 α ⁺ -thalassemia, Hb Constant Spring and Hb Paksé.
(Copyright © 2019 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)