Aims Krüppel-like factor 1 (KLF1) is an erythroid-specific transcription factor playing an important role in erythropoiesis and haemoglobin (Hb) switching. Biallelic KLF1 mutations can cause haemolytic anaemia with thalassaemia-like syndromes but are rarely reported. We explore the KLF1 mutations in Thai subjects with unexplainable haemolytic anaemia. Methods The study was done on 57 subjects presented with haemolytic anaemia and elevated Hb F without β-thalassaemia diseases. Hb analysis was performed using capillary electrophoresis. Analyses of α-thalassaemia, β-thalassaemia and KLF1 genes were performed using PCR-based methods and DNA sequencing. Results Thirteen subjects with compound heterozygous for a known and five new genetic KLF1 interactions were identified, including KLF1:c.519_525dupCGGCGCC/c.892G>C with class 3/2 (n=8), and each subject with new genetic interaction, including KLF1:c.-154C>T;643C>T/c.983G>A with class 3/2, KLF1:c.-154C>T;643C>T/c.809C>G with class 3/2, KLF1:c892G>C/c.983G>A with class 2/2, KLF1:c.892G>C/c.1001C>G with class 2/2 and KLF1:c.1001C>G/c.1003G>A with class 2/2. Most of them had anaemia with Hb levels ranging from 45 to 110 g/L, hypochromic microcytosis, aniso-poikilocytosis, increased Hb F levels (17.9%–47.4%), small amounts of Hb Bart’s, regular blood transfusion, hyperbilirubinaemia, increased serum ferritin and nucleated red blood cell. Conclusions Biallelic KLF1 mutations associated with anaemia may not be uncommon in Thailand. Characteristics of haemolytic anaemia, abnormal red cell morphology with nucleated red blood cells and elevated Hb F, and presenting small amounts of Hb Bart’s without thalassaemia diseases are useful markers to further investigation of the KLF1 gene.

Variants of uncertain significance (VUS) are often challenging for genetic counseling and require additional data for accurate variant classification. This study aims to describe the genotype-phenotype correlation of the seven β-globin gene variants found in Thailand. Retrospective data in a total of 45,914 subjects encountered at our diagnostic laboratory from January 2012 to December 2024 were reviewed. A total of 33 leftover EDTA blood specimens, suspected of having β-globin gene defects, were included. Eighty-nine normal subjects were also analyzed to confirm phenotypic expression of the variants. The whole β-globin and Krüppel-like factor 1 (KLF1) genes were examined using PCR-based methods. Seven nucleotide variants were identified among 33 suspected subjects, including a novel (β^−206(C>G)), four hitherto undescribed in Thailand [β^−198(A>G), β^{IVSII−180(T>C)}, β^{IVSII−337(A>G)}, and β^*233(G>C)], and two known variants [β^−50(G>A) and β^{IVSII−258(G>A)}]. The β^−198(A>G) and β^*233(G>C) variants were also identified in 1.69% of normal subjects, indicating neutral DNA polymorphisms. All subjects of β^−198(A>G), β^{IVSII−180(T>C)}, β^{IVSII−258(G>A)}, and β^{IVSII−337(A>G)} with borderline Hb A₂ levels had KLF1 mutations. Compound heterozygous β^−206(C>G) and known β⁺-thalassemia trait revealed β-thalassemia trait phenotype. In silico pathogenicity prediction showed that the β^−206(C>G), β^−198(A>G), β^{IVSII−180(T>C)}, β^{IVSII−258(G>A)}, β^{IVSII−337(A>G)}, and β^*233(G>C) were associated with benign variants. It was found that heterozygous β^−50(G>A) had elevated Hb A₂ levels resembling those of β-thalassemia trait. However, the association of the β^−50(G>A) and Hb E or β-thalassemia revealed a phenotype of Hb E or β-thalassemia trait. Most prediction tools indicate that the β^−50(G>A) is associated with benign variants; however, PromoterAI revealed that the β^−50(G>A) is associated with under-expression of the β-globin gene with high sensitivity. Based on these findings, the β^−50(G>A) is most likely a very mild β⁺-thalassemia allele. This study described the genotype-phenotype correlation of known and novel β-globin gene variants found in Thailand. The data should prove useful for accurate variant classification, genetic counseling, and a prevention and control program of severe thalassemia diseases in Thailand.

Background. Melioidosis is a severe infection caused by Burkholderia pseudomallei and is endemic in regions with a high prevalence of thalassemia. Patients with thalassemia are thought to be at increased risk due to iron overload, splenectomy, and immune dysfunction. However, the pooled prevalence and mortality outcomes of melioidosis in this population remain unclear. Methods. We conducted a systematic review and meta-analysis in accordance with PRISMA 2020 guidelines (PROSPERO: CRD420251108294). PubMed, Embase, and Scopus were searched from inception to July 2025. Observational studies reporting prevalence or mortality of melioidosis in patients with thalassemia were eligible. Pooled odds ratios (ORs) for mortality were calculated using random-effects models, with subgroup and sensitivity analyses based on age, thalassemia subtype, and study quality. Results. Six retrospective studies including 7529 melioidosis patients, of whom 173 had thalassemia, were analyzed. The prevalence of thalassemia among melioidosis cases ranged from 0.5% to 40.7%. Mortality among thalassemia patients varied from 0% to 100%. Pooled analysis demonstrated no significant excess mortality compared with non-thalassemia controls (OR 0.55, 95% CI 0.16–1.89; I² = 44.9%). Sensitivity analysis restricted to moderate- and high-quality studies showed a significantly lower risk of death (OR 0.23, 95% CI 0.15–0.36; I² = 0%). Subgroup analyses by thalassemia subtype and age revealed no clear effect modification, although power was limited. Conclusions. Despite biological plausibility, thalassemia was not associated with increased melioidosis mortality. These findings suggest that closer clinical monitoring, iron chelation, and comorbidity profiles may influence outcomes. Prospective, well-characterized cohort studies are needed to refine risk stratification and guide management in endemic regions.

Background: Many globin chain variants were interpreted as β-thalassemia or hereditary persistence of fetal hemoglobin (HPFH) at routine investigation. We described this in a large cohort of Thai subjects. Methods: Hematological data of 43,414 subjects encountered at our thalassemia diagnostic center from January 2013 to July 2025 were reviewed. A total of 372 subjects with hemoglobin (Hb) variants were selectively recruited with leftover DNA specimens for further analysis. Hb analysis was done using high-performance liquid chromatography (HPLC) or capillary electrophoresis. β-globin gene mutations were identified using PCR and related techniques. Results: Among 372 subjects recruited, a total of 21 different Hb variants were found. The levels of Hb A ₂ , Hb F, Hb variants, and DNA diagnostic requests were recorded. Hb variants with normal Hb A ₂ and Hb F levels were requested for β-thalassemia or HPFH in 12.3% (95% CI = 7.9–16.8). This error was increased in Hb variants with Hb A ₂ ≥ 3.6% [50.6% (95% CI = 39.8–61.4) and odds ratio of 7.3 (3.6–13.8)] and Hb F ≥ 5.0% [52.2% (95% CI = 37.7–66.6) and odds ratio of 7.8 (3.6–16.7)], especially in those with Hb A ₂ ≥ 3.6% and Hb F ≥ 5.0% [71.9% (95% CI = 56.3–87.5) and odds ratio of 18.2 (7.1–48.9)]. Hbs Hope, Tak, Cook, C, Lepore, and Q-Thailand were found to be associated with high proportions of the error. Conclusions: Hb variants with increased Hb A ₂ levels and/or co-migration with Hb F are associated with a high proportion of mis-interpretation of β-thalassemia in routine practice. Combining Hb analysis using two different methods, and molecular analysis should help improve laboratory interpretation of the cases.