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β-Thalassemia is a genetic disease characterized by reduced or non-functionality of β-globin gene expression, which is caused due to a number of variations and indels (insertions and deletions). In this case study, we have reported a rare occurrence of compound heterozygosity of two different variants, namely, HBBc.92G>C and HBBc.92+5G>C in materna...
Citations
... Another study reported rare compound heterozygosity of two different variants, namely HBBc.92GNC and HBBc.92+5GNC, in maternal amniotic fluid sample of a Gujarati family [20]. In this study, the nucleotide sequencing method was used to detect prenatal β-thalassemia mutation in fetal DNA. ...
Thalassemia is a hereditary blood disorder. It occurs due to two mutations in the HBB gene located on chromosome 11. This gene has 1606 base pairs and contains three exons. Moreover, HBB gene codes for β globin protein have been identified to posses 868 mutations, which comprise point mutation, insertion, deletion, and gene arrangement. In β thalassemia major, both alleles are mutated and no β chain is synthesized. In this study, three human families with thalassemia were selectedfrom different areas of Balochistan. For DNA extraction and estimation, 5 ml blood samples were extracted intravenously from the affected individuals, their normal siblings, and parents in 15ml falcon tubes containing 200μl EDTA. Primer sequences were designed on primer 3 for the mutational analysis of the HBB gene. Since the gene has a total of three exons and two introns, three primers, namely HBBX1, HBBX2 and HBBX3, were designed. These primers were used to amplify the HBB gene responsible for β thalassemia in all family samples. The amplified product was sequenced through an automated 3100 ABI Prism DNA sequence. The sequencing results were analyzed by the SaqMan software. This was done to determine if any genetic variable in the selected families showed mutations. In Family 1, 1 bp substitution mutation (c.9T>C) (p.his3his) and 1bp insertion (c.111T>G) (p.Ser10 val) in exon 1 of HBB gene were identified in thalassemia locus, while in in Family 2, 1bp substitution mutation (c.9T>C) (p.His3His) in exon 1 of HBB gene was identified in thalassemia locus. No mutation was observed in Family 03after sequencing.
... Persons with thalassemia major usually come to medical attention within the first two years of life. These patients re quire lifelong RBC transfusions at regular intervals to survive [7]. ...
β-thalassemia is common genetic disorders in Turkey that characterized by the reduced synthesis (β+) or absence (βo) of the β-globin chains in the HbA molecule. In this study, we aimed to determine the effect of the mutation type of the β-globin gene on hematological values in homozygous β-thalassemia. This retrospective study was undertaken by Prenatal Diagnosis Centres of Cukurova University Medical Biochemistry at Adana. We evaluated 60 homozygous by implementing DNA sequencing analysis for mutations undetectable by conventional methods. 30 patients with βo [FSC 44/ C-A] mutations and the other 30 patients with βo [(IVS-II-1(G>A), CD39 (C>T), Cd8 (-AA) Cd39 C> T and CD36/37 (–T)] mutations, totally 60 patients were included in the study. Erythrocyte indices, HbF, HbA2 levels were compared between the two groups. FSC 44/(-C) mutations were detected in patients. Hb, Hct, MCV in this group values were statistically lower than in patients with other detected mutations (P < 0.05). Between the two groups, there is no statistically different RBC, MCH, MCHC, HbF, HbA2 levels (P ˃ 0.05). For the first time in this study, it was found that the Hb, Hct and MCV value of the persons who carried the FSC 44/(-C) mutation were significantly lower than the persons who carrying other mutations. Between the two groups, there was no statistical difference in RBC, MCH, MCHC, HbF and HbA2 levels. Awareness of FSC/44 mutation, which may have a heterogeneous clinical presentation, is required. We herein present the hematologic findings of a Turkish population carrying this mutation. This will also help to make a diagnosis.
... Persons with thalassemia major usually come to medical attention within the first two years of life. These patients re quire lifelong RBC transfusions at regular intervals to survive [7]. ...
... This case was of the third pregnancy, earlier to this the family had two children, elder one was carrying same compound heterozygous mutations whereas younger child was thalassemia minor. Family history provided by the patients during the counseling suggested that the first child was having the symptoms similar thalassemia major, so their current pregnancy will also be thalassemia major because of the same genotype [31]. ...
About 200 causative mutations are characterized in the β-globin gene. Beta thalassemia diagnosis is very complicated due to the genetic diversity of HBB gene across different geographical regions of the world. In the present study, we have analyzed 138 clinical specimens among them 66 were from 21 unrelated families (trio samples which had DNA from father, mother and chorionic villus sample/amniotic fluid sample) and 72 individual specimens using newly developed sequencing and PCR based assay. We observed 11 different HBB gene mutations in 138 samples, which were also cited by literature as the most prevalent mutations in Indian subcontinent population. The most common mutation observed in our study was HBB.C.92+5 G>C (GC+CC genotype was observed to be 44.93%). Few interesting case studies like co-inheritance of sickle cell anemia and β- thalassemia traits, compound heterozygosity of beta thalassemia major mutation in the case of twin pregnancy were also focused briefly. Commercially available molecular diagnostic kits of HBB gene can detect and identify targeted mutations but will not detect novel and non-targeted mutations of beta thalassemia in parental blood and fetal samples. Hence, a screening technique involving complete sequencing of HBB gene (β-globin gene) is required along with gap PCR approach to provide complete diagnosis of beta thalassemia disease.
Background
A high incidence of thromboembolic events is observed in thalassemia patients. This study investigated the relationship between carotid intima-media thickness (CIMT) and lipid profile, iron metabolic indices (IMI), and inflammatory markers in β-thalassemia intermedia (β- TI) patients.
Research design and methods
Forty-five β-TI patients at Assiut University Hospital and thirty-four healthy individuals were enrolled in the study. We measured Lipid profile, IMI, high sensitive CRP (Hs-CRP), and interleukin-6 (IL-6) and compared the results between both groups. We used CIMT measurement as a marker for subclinical atherosclerosis. We used both univariate and multivariate analyses to test relations and independent predictors of CIMT.
Results
β- TI patients had higher CIMT (P = 0.000). CIMT was positively correlated with absolute neutrophil count (ANC) (r = 0.320, p = 0.032), ferritin (r = 0.544, p = 0.000), Hs-CRP (r = 0.603, p = 0.000), and IL-6 (r = 0.520, p = 0.000). Hs-CRP was an independent predictor of CIMT (p = 0.000). Hs-CRP cut off value of 60.4 ug/dl has sensitivity of 63.3% and specificity of 93.3% in predicting premature atherosclerosis.
Conclusion
β- TI patients had higher CIMT despite the protective lipid profile. Hs-CRP was an independent predictor of CIMT.
There is overwhelming evidence implicating Haemoglobin Subunit Beta (HBB) protein in the onset of beta thalassaemia. In this study for the first time, we used a combined SNP informatics and computer algorithms such as Neural network, Bayesian network, and Support Vector Machine to identify deleterious non-synonymous Single Nucleotide Polymorphisms (nsSNPs) present in the HBB gene. Our findings highlight three major mutation points (R31G, W38S, and Q128P) within the HBB gene sequence that have significant statistical and computational associations with the onset of beta thalassaemia. The dynamic simulation study revealed that R31G, W38S, and Q128P elicited high structural perturbation and instability, however, the wild type protein was considerably stable. Ten compounds with therapeutic potential against HBB were also predicted by structure-based virtual screening. Interestingly, the instability caused by the mutations was reversed upon binding to a ligand. This study has been able to predict potential deleterious mutants that can be further explored in the understanding of the pathological basis of beta thalassaemia and the design of tailored inhibitors.
A report in a Gujarati family in Western India consisting of rare co-inheritance of β-thalassemia (β⁰/β⁺) in a proband, son was identified. The trio samples, parents and son, of extracted DNA from blood were subjected to gene sequence analysis, electrophoretic pattern of Hb levels and blood indices. The proband (son) showed altered levels of Hb types with higher levels of HbF (90%) and low values of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) supporting β-thalassemia major. This case also possessed a compound heretozygotic condition c.92+5 G>C and c.47 G>A (β⁰/β⁺). Based on these markers, the proband was suggested blood transfusion by the clinician. Hence, it is suggested that this family must undergo prenatal diagnosis for the next pregnancy to avoid such risky condition.
