The Global Globin Network (GGN) is a project-wide initiative of the Human Variome/Global Variome Project (HVP) focusing on haemoglobinopathies to build the capacity for genomic diagnosis, clinical services, and research in low- and middle-income countries. At present, there is no framework to evaluate the improvement of care, treatment, and prevention of thalassaemia and other haemoglobinopathies globally, despite thalassaemia being one of the most common monogenic diseases worldwide. Here, we propose a universally applicable system for evaluating and grouping countries based on qualitative indicators according to the quality of care, treatment, and prevention of haemoglobinopathies. We also apply this system to GGN countries as proof of principle. To this end, qualitative indicators were extracted from the IthaMaps database of the ITHANET portal, which allowed four groups of countries (A, B, C, and D) to be defined based on major qualitative indicators, supported by minor qualitative indicators for countries with limited resource settings and by the overall haemoglobinopathy carrier frequency for the target countries of immigration. The proposed rubrics and accumulative scores will help analyse the performance and improvement of care, treatment, and prevention of haemoglobinopathies in the GGN and beyond. Our proposed criteria complement future data collection from GGN countries to help monitor the quality of services for haemoglobinopathies, provide ongoing estimates for services and epidemiology in GGN countries, and note the contribution of the GGN to a local and global reduction of disease burden.

(1) Background: Alpha (α)-thalassaemia is a genetic disorder that affects 5% of the world population. Deletional or nondeletional mutations of one or both HBA1 and HBA2 on chromosome 16 will result in reduced production of α-globin chains, a component of haemoglobin (Hb) that is required for the formation of red blood cells (RBCs). This study aimed to determine the prevalence, haematological and molecular characterisations of α-thalassaemia. (2) Method: The parameters were based on full blood count, high-performance liquid chromatography and capillary electrophoresis. The molecular analysis involved gap-polymerase chain reaction (PCR), multiplex amplification refractory mutation system-PCR, multiplex ligation-dependent probe amplification and Sanger sequencing. (3) Results: With a total cohort of 131 patients, the prevalence of α-thalassaemia was 48.9%, leaving the remaining 51.1% with potentially undetected α gene mutations. The following genotypes were detected: -α^3.7/αα (15.4%), -α^4.2/αα (3.7%), --^SEA/αα (7.4%), α^CSα/αα (10.3%), α^Adanaα/αα (0.7%), α^{Quong Szeα}/αα (1.5%), -α^3.7/-α^3.7 (0.7%), α^CSα/α^CSα (0.7%), -α^4.2/α^CSα (0.7%), –^SEA/α^CSα (1.5%), –^SEA/α^{Quong Sze}α (0.7%), -α^3.7/α^Adanaα (0.7%), --^SEA/-α^3.7 (2.2%) and α^CSα/α^Adanaα (0.7%). Indicators such as Hb (p = 0.022), mean corpuscular volume (p = 0.009), mean corpuscular haemoglobin (p = 0.017), RBC (p = 0.038) and haematocrit (p = 0.058) showed significant changes among patients with deletional mutations, but not between patients with nondeletional mutations. (4) Conclusions: A wide range of haematological parameters was observed among patients, including those with the same genotype. Thus, a combination of molecular technologies and haematological parameters is necessary for the accurate detection of α-globin chain mutations.

We report the haematological parameters and molecular characterization of beta zero (β°) South East Asia (SEA) deletion in the HBB gene cluster with unusually high levels of Hb F compared to a classical heterozygous beta zero (β°)-thalassaemia.Methods: Retrospective study on 17 cases of (β°) South East Asia (SEA) deletion from 2016 to 2019 referred to Institute for Medical Research were conducted. The clinical information and haematological profiles were evaluated. The mutation was analyzed, and the results were compared with other β°-thalassaemia groups. For HBB gene genotyping, all the cases were subjected for multiplex gap-PCR, 5 cases were subjected for HBB gene sequencing for exclusion of compound heterozygous with other beta variants. Co-inheritance of α-thalassaemia were determined using multiplex gap-PCR and multiplex ARMS-PCR.Results: Seventeen cases were positive for β°-thal SEA deletion. Fifteen cases were heterozygous and two were compound heterozygous for β°-thal SEA deletion. The results were compared with 182 cases of various heterozygous β° deletions and mutations. The mean Hb for heterozygous β°-thal SEA deletion (13.44 ± 1.45 g/dl) was normal and significantly higher than heterozygous IVS 1-1 and Codon 41/42 (post hoc test, p < 0.05). The medians for the MCV and MCH of β°-thal SEA deletion were significantly higher than for all heterozygote β°-thalassaemia traits (Mann Whitney test, p < 0.05). Patients with β°-thal SEA deletion had elevated levels of Hb A2 consistent with β-thalassaemia traits, with Hb F levels consistent with HPFH or δβ-thalassaemia carriers. The median for Hb A2 was 4.00 + 1.00%, similar to that observed in other β°-thalassaemia groups except for IVS 1-1 mutation (median 5.30 + 0.45%) and β°-Filipino (∼45 kb deletion) deletion (median 6.00 + 0.58). Interestingly, we found that Hb F levels for β°-thal SEA deletion were statistically higher than other β°-thalassaemia mutations (median 19.00 + 5.50%, p < 0.05), except for the β°-thal 3.5 kb deletion group.Conclusion: We conclude that β°-thal SEA deletion has a unique haematological parameters of beta zero thalassaemia trait. We affirm to classifying this deletion as SEA-HPFH based on previous studies considering the phenotype features rather than the molecular defect of β°-thal SEA deletion, as this will make it easier to offer genetic counselling to affected individuals.

Haemoglobinopathies remain a major public health challenge, predominantly in endemic regions. Increasing migration has extended their prevalence in previously non-endemic areas, complicating early detection and prevention. As part of the HELIOS CA22119 COST Action Working Group 1, this narrative review critically examines established and emerging laboratory techniques for haemoglobinopathy carrier detection. It also explores diagnostic limitations, regional disparities, and opportunities for global harmonisation to support early detection, prevention, and equitable care. A literature search of MEDLINE, PubMed, Scopus, and EMBASE (2014–2024) identified studies on the screening, diagnosis, and prevention of haemoglobinopathies. Findings were synthesised across three domains: (1) preventive strategies, (2) carrier screening methods, and (3) prenatal diagnostic approaches. Advances in molecular technologies have improved diagnostic sensitivity and specificity. However, conventional haematological approaches, particularly complete blood count and haemoglobin typing, remain essential and cost-effective first-line tools. Key challenges include unequal access to advanced diagnostics and the lack of standardised protocols across regions. Strengthening prevention requires coordinated global efforts to promote accessible, accurate, and standardised diagnostic approaches tailored to regional genomic, economic, and healthcare contexts. Early and equitable carrier detection, combined with effective prenatal diagnosis, is critical to reducing the global burden and improving health outcomes in both endemic and emerging regions.

BACKGROUND: β-thalassaemia has heterogeneous disease severities ranging from mild to trait, and major. Long noncoding RNAs (lncRNAs) are known to regulate microRNAs (miRNAs) and genes, possibly modifying the disease phenotypes. However, limited data exist on the lncRNAs in β-thalassaemia, and no study has yet addressed this gap in Malaysia. Therefore, this study aimed to identify the expression profile of lncRNAs in β-thalassaemia major and trait among Malaysians.METHODS: Case-control study was conducted in two phases at Tunku Azizah Women and Children's Hospital and the Institute of Medical Research, from September 2019 to November 2021. Total of 141 individuals were recruited, comprising β-thalassemia major (MAJOR, n=11), β-thalassemia trait (TRAIT, n=17), and healthy controls (CON, n=113). All participants were genotyped for thalassaemia and assessed for their haemoglobin and red blood cells (RBC) indices. In the first phase, discovery of lncRNA was performed using microarray, and differential expression of lncRNAs (DEL) in MAJOR, TRAIT, and CON groups was identified. Significant lncRNAs were subjected to lncRNA-miRNA prediction, and gene ontology and biological pathway were analyzed. In validation phase, six potential lncRNAs were further validated via using lncRNA polymerase chain reaction (PCR) custom array.RESULTS: Total of 364 DELs were identified in MAJOR group, and 128 DELs were identified in TRAIT group. Between the MAJOR and TRAIT groups, 100 DELs were dysregulated in MAJOR group. Two molecular networks comprising the lncRNA interactions with miRNAs were identified and associated with traits and major phenotypes, resulting in six potential lncRNAs for validation. Among these six lncRNAs, three lncRNAs (TYMSOS, VASH1-AS1, and LINC01001) were reduced in the MAJOR group (fold change (FC)=-6.67, p=0.026; FC=-8.33, p=0.022; and FC=-8.33, p=0.021, respectively).CONCLUSION: Expressions of TYMSOS, VASH1-AS1, and LINC01001 lncRNAs were altered differently between β-thalassaemia major and trait patients. Therefore these lncRNAs may serve as novel biomarkers for β-thalassaemia disease severity in Malaysian population.KEYWORDS: β-thalassaemia, lncRNAs, miRNAs, severity, major, trait, molecular network