Prenatal Screening for Co-Inheritance of Sickle Cell Anemia and β-Thalassemia Traits

Dhawan, Dipali; Chaudhary, Spandan; Chandratre, Khyati; Ghosh, Arpita; Sojitra, Niraj; Hirapara, Sandip; Singh, Sanjay Kumar; Bagali, Prashanth

doi:10.4172/2471-2663.1000108

Cited by 3 publications

(3 citation statements)

References 12 publications

(10 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Out of 21 trio samples screened, one of the amniotic fluid sample from a family study was identified with compound heterozygosity of sickle cell mutation as well as beta thalassemia mutation, developing severe symptoms in the patient, similar to beta thalassemia major, similar compound heterozygosity was observed with three individual samples also [28]. Individual with single mutation in heterozygous state can be non-symptomatic or normal but patient with compound heterozygous mutation in case of beta thalassemia exhibits symptoms similar to thalassemia major.…”

Section: Discussionmentioning

confidence: 88%

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

Chaudhary¹,

Dhawan²,

Sojitra³

et al. 2017

Biol Med (Aligarh)

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 88%

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

Chaudhary¹,

Dhawan²,

Sojitra³

et al. 2017

Biol Med (Aligarh)

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although, we have analyzed more than 15 families (trio samples) for β-thalassemia mutations, we have never found compound heterozygous β + β 0 type mutations in native Gujarati families. We have observed co-inheritance of β-thalassemia mutation (HBBc.92 + 5G > C) and sickle cell anemia disease causing mutation (HbE) in the amniotic fluid of parents, who were carriers [9] . Ambekar et al has reported similar case of compound heterozygous state of β-thalassemia mutations in the Maharashtrian population of India [10] .…”

Section: Discussionmentioning

confidence: 99%

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

Chaudhary¹,

Dhawan²,

Bagali³

et al. 2016

Molecular Genetics and Metabolism Reports

Self Cite

View full text Add to dashboard Cite

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 maternal amniotic fluid sample. Prenatal β-thalassemia mutation detection in fetal DNA was carried out using nucleotide sequencing method. After analysis, the father was found to be heterozygous for HBBc.92G > C (Codon 30 (G > C)) mutation which is β0 type and the mother was heterozygous for HBBc.92 + 5G > C (IVS I-5 (G > C)) mutation which is β+ type. When amniotic fluid sample was analyzed for β-globin gene (HBB), we found the occurrence of heterozygous allelic pattern for aforesaid mutations. This compound heterozygous state of fetus sample was considered as β+/β0 category of β thalassemia which was clinically and genotypically interpreted as β-thalassemia major. Regular blood transfusions are required for the survival of thalassemia major patients hence prenatal diagnosis is imperative for timely patient management. Prenatal diagnosis helps the parents to know the thalassemic status of the fetus and enables an early decision on the pregnancy. In the present study, we have identified compound heterozygosity for β-thalassemia in the fetus which portrays the importance of prenatal screening.

show abstract

“…The two types of thalassemia (alpha thalassemia and beta thalassemia) have the manner in inheriting the disease [7].…”

Section: Thalassemia In Heritancementioning

confidence: 99%

Genetics and Epigenetics Aspects of Thalassemia

Putri¹,

Gultom²,

Auerkari³

2022

Proceedings of the 4th International Conference on Life Sciences and Biotechnology (ICOLIB 2021)

View full text Add to dashboard Cite

Hemoglobin contains of heme, which binds iron and protoporphyrin, and globin, which consist of combination of α, β, δ, and γ chain. α-globin globin gene is located in 16p13.3 cytogenetically, and β-globin gene is in 11p15.4. Thalassemia is a blood disorder characterized in the lack or absence of one of globin chain. Thalassemia is classified as alpha thalassemia and beta thalassemia depending on which globin chain is reduced. Alpha thalassemia occurs when alpha globin chain in chromosome 16 is reduced or absence due to removal or deletion in the molecular level. Alpha thalassemia itself has several types including alpha thalassemia silence carrier, alpha thalassemia minor, haemoglobin H disease, and Hydrops fetalis. Alpha thalassemia silence carrier and alpha thalassemia minor is clinically asymptomatic. Hemoglobin H disease shows moderate to severe anemia symptom, while Hydrops fetalis is fatal. The reduced or absence of alpha globin chain causing the excess of beta globin chain. Beta thalassemia occur when beta globin chain synthesis is compromised mainly because of point mutation in chromosome 11. Beta thalassemia is divided into beta thalassemia minor, intermedia, and major. Beta thalassemia minor is clinically asymptomatic, while intermedia type shows symptoms between the minor and the major. Beta thalassemia major is the most severe among beta thalassemia, and regular blood transfusion may be needed of the anemia symptoms are increased. Besides genetic factors, epigenetic factors also play roles in causing thalassemia. Treatment of thalassemia is depended on its symptoms, such as blood transfusion and surgical treatment. Genetic therapy for thalassemia is still in development of therapy options.

show abstract

Prenatal Screening for Co-Inheritance of Sickle Cell Anemia and β-Thalassemia Traits

Cited by 3 publications

References 12 publications

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

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

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

Genetics and Epigenetics Aspects of Thalassemia

Contact Info

Product

Resources

About