title: Compound heterozygous β(+) β(0) mutation of HBB gene leading to β-thalassemia major in a Gujarati family - A case study.
abstract: 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 β(0) 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(+)/β(0) 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.
authors.affiliation: Medical Genetics and Diagnostics Division, Xcelris Labs Ltd., Old Premchand Nagar Road, Opp. Satyagrah Chhavani, Bodakdev, Ahmedabad 380015, Gujarat, India.
authors.forename: Spandan
authors.initials: S
authors.lastname: Chaudhary
authors.affiliation: Medical Genetics and Diagnostics Division, Xcelris Labs Ltd., Old Premchand Nagar Road, Opp. Satyagrah Chhavani, Bodakdev, Ahmedabad 380015, Gujarat, India.
authors.forename: Dipali
authors.initials: D
authors.lastname: Dhawan
authors.affiliation: Medical Genetics and Diagnostics Division, Xcelris Labs Ltd., Old Premchand Nagar Road, Opp. Satyagrah Chhavani, Bodakdev, Ahmedabad 380015, Gujarat, India.
authors.forename: Prashanth G
authors.initials: PG
authors.lastname: Bagali
authors.affiliation: NGS Department, Xcelris Labs Ltd., Old Premchand Nagar Road, Opp. Satyagrah Chhavani, Bodakdev, Ahmedabad 380015, Gujarat, India.
authors.forename: Pooja
authors.initials: P
authors.lastname: S Chaudhary
authors.affiliation: Medical Genetics and Diagnostics Division, Xcelris Labs Ltd., Old Premchand Nagar Road, Opp. Satyagrah Chhavani, Bodakdev, Ahmedabad 380015, Gujarat, India.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Chaudhary
authors.affiliation: Sanger Sequencing Division, Xcelris Labs Ltd., Old Premchand Nagar Road, Opp. Satyagrah Chhavani, Bodakdev, Ahmedabad 380015, Gujarat, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Singh
authors.affiliation: NGS Department, Xcelris Labs Ltd., Old Premchand Nagar Road, Opp. Satyagrah Chhavani, Bodakdev, Ahmedabad 380015, Gujarat, India.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Vudathala
keywords: Amniotic fluid; Compound heterozygous; Nucleotide sequencing; β+/β0 mutation; β-Thalassemia