Haplotype Analysis of β-Thalassaemia Major and Carriers with Filipino β°-Deletion in Sabah, Malaysia

Abstract

ObjectiveThe Filipino β°-deletion has been reported as a unique mutation in East Malaysia with a severe phenotype due to the complete absence of β-globin chain synthesis. In this study, the haplotype patterns of the β-globin gene cluster were used to relate the human genetic variation to this specific β-thalassaemia mutation.MethodsThe 376 study subjects included 219 β-thalassaemia major (β-TM) patients with homozygous Filipino β°-deletion and 157 carriers with heterozygous Filipino β°-deletion from 10 government hospitals in different regions of Sabah. Genomic DNA was isolated from whole blood using silica membrane based DNA purification protocol. Polymerase chain reaction restriction fragment length polymorphism analysis (PCR-RFLP) was conducted on five markers within the β-globin gene cluster to construct the haplotype patterns.ResultsFour haplotypes (Haplotype I–IV) were identified with Haplotype I as the predominant haplotype with the highest frequency of 0.98, followed by Haplotype II, III and Haplotype IV with 0.02. Haplotype I was strongly linked with the Filipino β°-deletion among the indigenous population.ConclusionHaplotype I as the predominant haplotype suggests the patients with the Filipino β°-deletion in Sabah have a similar origin.

Molecular basis of a high Hb A2/Hb Fβ-thalassemia trait: a retrospective analysis, genotype-phenotype interaction, diagnostic implication, and identification of a novel interaction withα-globin gene triplication

“…This Filipino β -thalassemia deletion [NG_000007.3:g.66258_184734del118477] was described originally as approximately 45 kb long starting from position -4,279 bp relative to the mRNA cap site of the β -globin gene but with an uncertain 3′ breakpoint. It was later described using gap-PCR and DNA sequencing as 118 kb in length, with the 5′ breakpoint at position −4,279 of mRNA cap site, and the 3′ breakpoint extending to the downstream olfactory receptor (OR) region where it deletes four functional OR genes and two OR pseudogenes including the OR52A1 that contains a γ -globin gene enhancer ( Yamsri et al, 2012 ; Teh et al, 2018 ; Yasin et al, 2022 ). Table 4 compared the hematological parameters of β 0 -thalassemia carriers with three different β -thalassemia deletions in our series, including the 3.4 kb deletion ( n = 103), the Filipino β 0 -thalassemia ( n = 9), and 105 bp β 0 -thalassemia deletion ( n = 7), all without α -thalassemia.…”