Compound heterozygous β+ β0 mutation of HBB gene leading to β-thalassemia major in a Gujarati family — A case study

Chaudhary, Spandan; Dhawan, Dipali; Bagali, Prashanth; Chaudhary, Pooja; Chaudhary, Anjali; Singh, Sanjay Kumar; Vudathala, Srinivas

doi:10.1016/j.ymgmr.2016.04.002

Cited by 6 publications

(3 citation statements)

References 11 publications

(12 reference statements)

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“…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.…”

Section: Discussionmentioning

confidence: 99%

Mutational Studies of Gene HBB in β-Thalassemia Patients from Balochistan, Pakistan

Nawaz

Yousafzai

Luqman

et al. 2021

CTO

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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.

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Section: Discussionmentioning

confidence: 99%

Mutational Studies of Gene HBB in β-Thalassemia Patients from Balochistan, Pakistan

Nawaz

Yousafzai

Luqman

et al. 2021

CTO

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“…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].…”

Section: Discussionmentioning

confidence: 99%

Whole Gene Sequencing Based Screening Approach to Detect β-Thalassemia Mutations

Chaudhary¹,

Dhawan²,

Sojitra³

et al. 2017

Biol Med (Aligarh)

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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.

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“…Several transcription factors bind and regulate the function of the HBB gene, the most important of which is erythroid Kruppel-like factor 1, which binds the proximal CACCC box [5]. The mutations of the HBB gene cause the abnormal formation of haemoglobin which leads to improper oxygen transportation and damage of red blood cells [6]. Patients with mutations in both HBB alleles that significantly reduce the HBB protein production suffer from severe anaemia and skeletal abnormalities [7].…”

Section: Introductionmentioning

confidence: 99%

Computational and drug target analysis of functional single nucleotide polymorphisms associated with Haemoglobin Subunit Beta (HBB) gene

Soremekun

Ezenwa

Isewon

et al. 2020

Computers in Biology and Medicine

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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.

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Compound heterozygous β+ β0 mutation of HBB gene leading to β-thalassemia major in a Gujarati family — A case study

Cited by 6 publications

References 11 publications

Mutational Studies of Gene HBB in β-Thalassemia Patients from Balochistan, Pakistan

Mutational Studies of Gene HBB in β-Thalassemia Patients from Balochistan, Pakistan

Whole Gene Sequencing Based Screening Approach to Detect β-Thalassemia Mutations

Computational and drug target analysis of functional single nucleotide polymorphisms associated with Haemoglobin Subunit Beta (HBB) gene

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