Thalassemia is the most common inherited hemoglobinopathy worldwide. Variation of clinical symptoms in this hemoglobinopathy entails differences in disease-onset and transfusion requirements. The aim of this study was to investigate the role of α-globin gene deletions in modulating the clinical heterogeneity of β-thalassemia (β-thal) syndromes. A total number 270 β-thal subjects were enrolled. Hematological parameters were recorded. β-Globin mutations were determined by amplified refractory mutation system-polymerase chain reaction (ARMS-PCR), gap-PCR and Sanger sequencing. α-Globin gene deletions were determined by multiplex PCR. Out of 270 β-thal subjects, 19 carried β⁺/β⁺, 74 had β⁰/β⁰ and 177 had the β⁰/β⁺ genotype. When we determined the severity of the different β-thal subjects in coinherited with the α gene deletion, it was revealed that, 84.2% β⁺/β⁺ subjects carried a non severe phenotype and did not have an α gene deletion. Of the β⁰/β⁰ individuals, 95.9% presented a severe phenotype, irrespective of α-globin gene deletions. In cases with the β⁰/β⁺ genotype, 19.2% subjects also carried a deletion on the α gene. Of these, 61.8% presented a non severe phenotype and 38.2% were severely affected. Only in the β⁰/β⁺ category did α gene deletions make a significant contribution (p < 0.001) toward alleviation of clinical severity. Therefore, it can be stated that α-globin gene deletions play a role in ameliorating the phenotype in patients with a β⁺/β⁰ genotype.

Dengue is the fastest-growing viral disease caused by an RNA virus, namely dengue virus, throughout India due to global warming. It has been declared a global threat by the World Health Organization due to the upsurge in cases as well as the deaths due to dengue over the last two decades. Most commonly, four serotypes of dengue viruses have high morbidity and mortality throughout the world. The major transmitting agents of this virus are the two species of the female Aedes mosquito, A. aegypti, and A. albopictus. In West Bengal, several outbreaks were reported at different times. Dengue-infected persons were categorized into different categories based on their clinical symptoms. Being a viral disease, it is only managed based on the clinical symptoms, and no specific drugs are available for the treatment of dengue patients. The common methods of management are fluid management and nutritional management to balance the body’s fluid and strengthen the body’s immunity. Several micronutrients, like vitamins D, E, and C, play a major role in dengue management. Other than these vitamins, micronutrients, like zinc and iron, were also successfully used for dengue management. At present, the only way to manage dengue patients is through supportive therapy and micronutrient supplementation.

Thalassemia is a common monogenic autosomal disorder prevalent in India. HbE beta thalassemia is a compound heterozygous state of two different beta globin mutations (HBB), predominant in the Eastern India. In HbE-beta thalassemia (β⁺/β°) patients, one HBB mutation does not produce any functional protein (β°); another mutation produces a structural altered haemoglobin, variant E (β⁺). It has been observed that in HbE-beta thalassemia patients with same type of HBB mutations, there exist diverse phenotypic presentation ranging from very severe, with regular transfusion-dependence to clinically non severe requiring very less transfusion or no transfusion. To explore this phenotypic mystery, we performed trio based expanded whole exome sequencing (WES) of two extreme phenotypes of HbE beta thalassemia subjects with similar HBB genotype and their parents. For WES library preparation, Agilent Sure select V6+UTR kit was used and sequencing was done through the Illumina HiSeq 2500 platform. This study aimed to search for de novo or inherited variants associated with the clinical severity. Six significant inherited variants were found in the genes, ATOH8, TTLL4, P2RX7, PRSS54, SLC9C2 and VRK2 in severe subject, however only one significant inherited variant in MTRR gene was found in non-severe subject. Bioinformatic analysis also confirms that each variant significantly changes in respective protein structure. The identified genes were either associated with iron absorption, oxidative stress, hematopoietic stem cell differentiation, structural organization of RBC cytoskeleton or regulating anemia. No significant de novo variant were identified associated with clinical severity. The finding of this study indicates that the combined effect of mutation load in major pathways may responsible for severe phenotype.

Thalassemia is the commonest inherited hemoglobinopathy worldwide. Variation of clinical symptoms entail differences in disease-onset and transfusion requirements. Our objective was to investigate the role of alpha gene deletions in modulating the clinical heterogeneity of thalassemia syndromes. A total of 214 individuals with diagnosed beta-thalassemia major/intermedia were included in the study. Beta globin mutations were determined and categorized as β ⁺ and β ⁰ . Eight common alpha globin gene deletions were detected by multiplex GAP-PCR. Out of the 17 individuals with β ⁺ /β ⁺ , 16 did not harbour alpha deletions (αα/αα), and most of them were non-severe. On the other hand, out of 46 individuals with β ⁰ /β ⁰ , 30 did not reveal alpha deletions, whereas 16 possessed one or more alpha deletion(s). Accordingly, most of them presented as clinically severe. Out of the 151 β ⁰ /β ⁺ individuals, 119 were negative for alpha deletion, whereas 32 possessed alpha deletions. It was observed that, only in this last category, alpha deletions made a significant contribution (P< 0.0001) in modulation of clinical non severity in this genotype. In conclusion, alpha globin gene deletions play a role to help in ameliorating the phenotype in the β ⁺ /β ⁰ genotype. However, they may have only minor/no role in patients with β ⁺ /β ⁺ or β ⁰ /β ⁰ genotype.

β-thalassemia patients often experience ocular abnormalities such as angioid streaks (ASs), retinal pigmented epithelium degradation, visual field defects, and in rare instances choroidal neovascularization (CNV). Although ASs are common in individuals with hemoglobinopathies, the occurrence of choroidal neovascularization without preceding ASs is exceptionally rare. In this report, we describe a β-thalassemia patient who had developed CNV at the age of 27 years and also had experience of renal stones at the age of 19 years. He had undergone splenectomy and was under conservative therapy of iron supplementation. We conducted whole-exome sequencing (WES) in search of CNV-associated variants. Through variant filtering and Phenolyzer analysis, we have identified a rare heterozygous missense variant in the ABCC6 gene, ABCC6:NM_001171:exon25:c.3524T>C (rs376062004). In silico analysis revealed that this variant is present in the highly conserved region and is likely to decrease the stability of the protein. Mutation in the ABCC6 gene leads to pseudoxanthoma elasticum (PXE). Previously, it was believed that ASs and subsequent CNV-like ocular complication may develop due to the pathophysiological condition of thalassemia. However, our study provides compelling evidence that rare mutations in the ABCC6 gene, in combination with oxygen insufficiency, may contribute to the development of CNV in β-thalassemia patients. This finding highlights the potential genetic basis of PXE-mediated CNV development in β-thalassemia.