From Genes to Therapy: A Comprehensive Exploration of Congenital Heart Disease Through the Lens of Genetics and Emerging Technologies.

Congenital heart disease (CHD) affects approximately 1% of live births worldwide, making it the most common congenital anomaly in newborns. Recent advancements in genetics and genomics have significantly deepened our understanding of the genetics of CHDs. While the majority of CHD etiology remains unclear, evidence consistently indicates that genetics play a significant role in its development. CHD etiology holds promise for enhancing diagnosis and developing novel therapies to improve patient outcomes. In this review, we explore the contributions of both monogenic and polygenic factors of CHDs and highlight the transformative impact of emerging technologies on these fields. We also summarized the state-of-the-art techniques, including targeted next-generation sequencing (NGS), whole genome and whole exome sequencing (WGS, WES), single-cell RNA sequencing (scRNA-seq), human induced pluripotent stem cells (hiPSCs) and others, that have revolutionized our understanding of cardiovascular disease genetics both from diagnosis perspective and from disease mechanism perspective in children and young adults. These molecular diagnostic techniques have identified new genes and chromosomal regions involved in syndromic and non-syndromic CHD, enabling a more defined explanation of the underlying pathogenetic mechanisms. As our knowledge and technologies continue to evolve, they promise to enhance clinical outcomes and reduce the CHD burden worldwide.

Unraveling Impact of Hemoglobin F and A2 Levels: Correlation With Disease Severity and Treatment Response in Transfusion-Dependent Beta-Thalassemia.

BACKGROUND: Fetal hemoglobin (HbF) has been reported to be associated with disease severity and treatment response to HbF-inducing therapies like Hydroxyurea and thalidomide in patients suffering from transfusion-dependent beta-thalassemia (TDT). However, the role of hemoglobin A2 (HbA2) remains less clear in TDT, therefore this study aims to determine the impact of both HbF and HbA2 levels on disease severity and treatment response. METHODOLOGY: A prospective observational study was conducted at the Peshawar Institute of Medical Sciences and Fatimid Foundation Peshawar from May 2023 to October 2023. A total of 232 TDT-diagnosed patients were enrolled using a convenient sampling technique, whereas coinheritance of beta-thalassemia with other hemoglobinopathies was excluded. RESULT: This study reveals a significant impact of HbF on disease severity (p<0.05) but finds no substantial correlation (p>0.05) between HbA2 levels and disease severity. Additionally, HbF and HbA2 levels exhibit no association with treatment response categories in patients receiving HbF induction therapy, and various mutations do not significantly alter HbF and HbA2 levels or disease severity parameters in TDT patients. CONCLUSION: The study established a significant association between HbF and disease severity. However, regarding treatment response, neither HbF nor HbA2 levels impact response categories. Combinatorial treatment with hydroxyurea and thalidomide showed superior efficacy compared to monotherapy. A larger sample size and extended follow-up are recommended to further explore the impact of HbF, HbA2, and various mutations on disease severity and treatment response.

Correlation Of Serum Ferritin With Haemoglobin A2 Level In Beta Thalassemia Traits.

BACKGROUND: Haemoglobin-A2 is considered as a paramount diagnostic parameter for the detection of beta-thalassemia trait which may vary with the fluctuation of body iron stores. The current study aims to evaluate the correlation of serum ferritin as a parameter of body iron stores with haemoglobin-A2 level in beta-thalassemia traits. METHODS: This cross-sectional study was conducted on total 134 known beta-thalassemia traits in Rehman Medical Institute-Peshawar, Pakistan from October 2018 to June 2019. Blood samples from the contributors were drawn in EDTA and plain tubes for complete blood counts, haemoglobin-A2 and serum ferritin estimation. Participants were categorized into 3 groups on the basis of iron status; beta-thalassemia traits with low ferritin (Group A), normal ferritin (Group B) and high ferritin levels (Group C). Pearson correlation was applied to analyse the correlation between the variables. RESULTS: Out of total 134 known beta-thalassemia traits, 73 (54.5 %) were males and 61 (45.5%) were females. Participants of group A with low ferritin were 22 (16.4%), group B with normal ferritin were 96 (71.6%) and group C with high ferritin were 16 (11.9%). Group A shows lowest mean haemoglobin-A2 level comparatively to Group B and Group C, with some effect of serum ferritin on haemoglobin-A2 level. CONCLUSIONS: Haemoglobin-A2 value decreases when there is a decrease in serum ferritin and show slightly increase with high ferritin level as compared to normal ferritin level or body iron stores in beta-thalassemia traits. However, this correlation is not significant enough to mask the actual diagnosis of the disease.

Co-existing iron deficiency/overload in beta-thalassemia trait.

OBJECTIVE: To identify the co-existence of iron deficiency and iron overload in individuals with beta thalassaemia trait. METHODS: The cross-sectional study was conducted at Rehman Medical Institute and Khyber Medical University, Peshawar, Pakistan, September 1, 2015, to December 31, 2017, and comprised individuals with hypochromic microcytic blood picture. Haemoglobin electrophoresis was performed on their blood samples. Serum ferritin levels of subjects with Haemoglobin Subunit Alpha 2 levels between 3.5% and 7% were checked. Data were analysed using analysed using GraphPad Prism v6. RESULTS: Of the 292 subjects, 159(54.5%) were males and 133(45.5%) were females. Of these, 240 (82.2%) were anaemic and 52 (17.8%) had haemoglobin within the normal range. Serum ferritin level of 55(18.8%) subjects was low and 207(70.9%) were iron-replete. Notably, 30(10.3%) subjects had serum ferritin levels higher than the reference range, and this was more common among adults (p<0.001). CONCLUSIONS: Ferritin levels in beta thalassaemia trait can be low, normal or higher than the normal values..

Frequency of ABH secretors and non secretors: A cross sectional study in Karachi.

OBJECTIVE: ABO blood group and secretor status is valuable in relation to some diseases in clinical and forensic medicine. Across the globe there are geographic and racial differences in the frequency of secretors and non-secretors. Aim of this study was to evaluate the status of ABH blood group secretors and non-secretors in Karachi (Pakistan). METHODS: Blood and saliva samples were randomly collected from one hundred and one (n=101) healthy adult students (76 male, 25 female) ranging in age from 15 to 40 years. Their ABO and Rhesus blood groups were determined by conventional methods, and their secretor status was studied by hemagglutination inhibition method of saliva. RESULTS: RESULTS showed that 64.4% of the study population were ABH blood group secretors while 35.6% were non-secretors. Frequencies of the secretor status among various ABO blood groups were 71.4% in group A, 79.5% in group B, 45.5% in group AB, and 61.5% in group O. CONCLUSION: Frequency of ABH secretor is high (64.4%). Blood group B has the highest secretor (79.5%) frequency while Blood group AB has the lowest (45.5%).