α- and ß-Globin Gene Mutations in Individuals with Hemoglobinopathies in the Chattogram and Sylhet Regions of Bangladesh.

Hemoglobinopathies, including α- and ß-thalassemias and sickle cell disease, are among the most widely disseminated hereditary blood disorders worldwide. Bangladesh is considered a hotspot for hemoglobinopathies, and these diseases cause a significant health concern in the country. However, the country has a dearth of knowledge on the molecular etiology and carrier frequency of thalassemias, primarily due to a lack of diagnostic facilities, limited access to information, and the absence of efficient screening programs. This study sought to investigate the spectrum of mutations underlying hemoglobinopathies in Bangladesh. We developed a set of polymerase chain reaction (PCR)-based techniques to detect mutations in α- and ß-globin genes. We recruited 63 index subjects with previously diagnosed thalassemia. Along with age- and sex-matched control subjects, we assessed several hematological and serum indices and genotyped them using our PCR-based methods. We identified that parental consanguinity was associated with the occurrence of these hemoglobinopathies. Our PCR-based genotyping assays identified 23 HBB genotypes, with the codons 41/42 (-TTCT) (HBB: c.126_129delCTTT) mutation leading the spectrum. We also observed the presence of cooccurring HBA conditions, of which the participants were not aware. All index participants in this study were on iron chelation therapies, yet we found they had very high serum ferritin (SF) levels, indicating inefficient management of the individuals undergoing such treatments. Overall, this study provides essential information on the hemoglobinopathy mutation spectrum in Bangladesh and highlights the need for nationwide screening programs and an integrated policy for diagnosing and managing individuals with hemoglobinopathies.

Lead and lead-arsenic combined exposure induces mortality and developmental impairments in zebrafish embryos: a study using wild-caught zebrafish from Bangladesh.

Heavy metal toxicity has become a global health burden, exerting various physiological effects on aquatic animals and humans. Zebrafish (Danio rerio) has emerged as a real-time model system for toxicological study. We previously reported the effects of arsenic on the embryonic development of zebrafish. The current study aimed to get deep insights into the toxic effects of another heavy metal, lead, on the early embryonic development of wild-caught zebrafish. We exposed freshly collected zebrafish embryos to different lead concentrations and studied different developmental and morphological changes using an inverted microscope. In a separate experiment, embryos were exposed to a combination of lead and arsenic to evaluate the combined effects of the elements. Lead concentration of as low as 0.25 mM resulted in developmental and morphological abnormalities in the zebrafish embryos. Exposure to different concentrations (0.25 mM, 0.5 mM, and 0.75 mM) caused a higher mortality rate of the embryos. Besides, an increased rate of arrested hatching, irregularities in size and shape of the yolk sac, deformed otic vesicle, and body curvature were observed in a dose-dependent manner. Lead exposure also resulted in reduced heart rate and severe pericardial edema. The combined effect of minimum concentrations of lead and arsenic that causes toxicity individually (0.25 mM and 1.0 mM, respectively) revealed a more severe effect than the individual treatments. This study's findings explain the association of heavy metal exposure with an increased rate of miscarriage/abortion incidences in highly polluted areas assisting in proper management and creating public awareness.

Arsenic hampered embryonic development: An in vivo study using local Bangladeshi Danio rerio model.

Zebrafish (Danio rerio) has appeared as a valuable and popular model species to study the developmental and toxicological impact of environmental pollutants. To get insights on the toxicological effect of arsenic on early embryonic development, a controlled breeding of local Bangladeshi zebrafish followed by comprehensive microscopic analysis was conducted to study the embryonic development after exposure to different concentrations of arsenic ranges from 4-120 h post-fertilization. Zebrafish embryos exposed to 2 mM of arsenic displayed distinguishable developmental delay compared to control. At three days post-fertilization, a distinct phenotype appears in arsenic-treated embryos, which can be characterized by dechorionated embryos, larger egg mass, pericardial edema, abnormal heart rate, and abnormal head development. Remarkably, the death rate of the arsenic-treated embryos was significantly higher compared to control. Collectively, these findings indicate that exposure to arsenic may result in abnormal embryonic development. These results suggest for proper management of the pregnant mother in the arsenic-exposed area, and may also explain the incidence of increased miscarriage/abortion rate in arsenic water drinking pregnant mother.