Mutation Analysis of Exon 1 in the Hemoglobin Subunit Beta (HBB) Gene in Beta-Thalassemia.

Introduction Thalassemia is a widely prevalent monogenic hematological disorder found worldwide. It exists in two forms: alpha- and beta-thalassemia. Alterations in the hemoglobin subunit beta (HBB) gene cause beta-thalassemia, with missense and point mutations affecting beta-globin synthesis. Consequently, genetic screening for beta-thalassemia is essential for genetic counseling, carrier screening, and prenatal diagnosis. Aim and objective This study aims to examine and identify mutations in the exon 1 region of the HBB gene in beta-thalassemia patients from the Vijayapura region. Methods This study involved 47 clinically diagnosed children with beta-thalassemia from a hospital in Vijayapura, India. Detailed clinical histories of all patients were recorded. Genomic DNA was extracted from the blood samples of these patients and subjected to polymerase chain reaction (PCR) using exon-specific primers for the HBB gene. The PCR products were then sequenced using the capillary-based Sanger sequencing method to identify mutations in the HBB gene. Results A total of 47 clinically diagnosed beta-thalassemia patients were included in the study, comprising 30 males and 17 females, aged between one and 20 years. Sequencing analysis of exon 1 in the beta-globin gene identified 17 beta-thalassemia variants. The most common mutation observed was T>G, G>C, C>A, and C>T in the exon 1 region of the HBB gene.  Conclusion This study identifies the pattern of beta-thalassemia mutations, aiding in the prevention of the disorder through prenatal diagnosis and genetic counseling. Mutations can alter codon sequences, affecting protein production. Research highlights the importance of a primary prevention program to analyze mutations and sequence variations at the molecular level, thereby helping to address numerous genetic disorders.

Variation in Exon 29 of the NOS1 Gene Does Not Contribute to Parkinson's Disease in the North Karnataka Population.

INTRODUCTION: Nitric oxide (NO) overproduction has been found to have neurotoxic effects on the brain. Moreover, in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced, the suppression of the NO-synthesizing enzymes, such as neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS), has neuroprotective benefits in Parkinson's disease (PD). These findings imply that NOS may have a role in regulating the nigral dopaminergic neurons' tolerance to environmental stressors in PD. OBJECTIVE: In the present study, we investigated variations in the NOS1 gene that may raise the likelihood of PD. METHODS: PD patients who visited the neurology departments of several medical colleges and hospitals in North Karnataka, India, between 2009 and 2011 were included in the study. The detailed clinic pathological details were obtained from 100 PD patients. Genomic DNA was isolated using the kit method followed by the evaluation of the quality and quantity of isolated gDNA. Polymerase chain reaction (PCR) amplification of exon 29 was performed, and sequencing was performed using the Applied Biosystems ABI 3500 Sanger sequencing platform. RESULTS: The present study is comprised of 100 PD patients, which includes 65 males and 35 females. There were 64 sporadic, 34 idiopathic, and two familial PD cases. The majority (67.1%) of PD cases were from metropolitan areas. Community-based segregation showed that the maximum cases were from Hindu Lingayat. A proportion (90.8%) of the patients had tremors, 32.7% of them displayed slowness in their daily tasks, and 8.1% of them had dyskinesia. Molecular analysis showed two untranslated region (UTR) variations g.151787 del T (rs1434015950) and g.151745 C>T (rs2682826) in our study group. CONCLUSION: The absence of mutations in the targeted NOS1 gene in the PD patients from North Karnataka shows the involvement of other genes in the molecular pathophysiology. Thus, it is crucial to screen other possible genes using cutting-edge technology to obtain a clear picture of the genetics of PD.

Molecular basis of ß-thalassemia in Karnataka, India.

In ß-thalassemia, point mutations in the ß-globin gene are largely responsible for either decreased or no ß-globin synthesis. The ß-globin gene has three exons and two introns. The molecular characterization of ß-thalassemia is absolutely necessary for carrier screening, for genetic counseling, and to offer prenatal diagnosis. The objective of the present study was to identify the rare mutations in ß-globin gene of ß-thalassemia patients. We have sequenced the entire ß-globin gene in 36 clinically identified thalassemia patients from the Karnataka region using polymerase chain reaction and sequencing. Our analysis revealed 11 ß-thalassemia variants. The most common being IVSII-16 G>C, IVSI-5G>C, IVSII-74 T>G, codon 3 (T>C), and Poly A site (T>C). In addition, we have also documented a novel deletion at codon 6 (-CT) (HBB:c.16delCT). These data are useful in future molecular screening of the population for implementing a thalassemia prevention and control program. Further it is found that family studies and comprehensive hematological analyses would provide useful insights for accurate molecular diagnosis of thalassemia phenotype and offers an interesting subject for further investigations in the Indian populations.