Spandan Chaudhary
Xcelris Labs, India
Title: Case Study on identification of compound heterozygous ß+ ß0 mutation of HBB gene leading to ß-thalassemia major in India
Biography
Biography: Spandan Chaudhary
Abstract
β-Thalassemia is a genetic disease characterized by reduced or non-functionality of β-globin gene expression, which is caused due to number of genetic variations and indels (insertions and deletions). In the present 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 was detected using nucleotide sequencing method. After analysis, the father was found to be heterozygous for HBBc.92G>C (Codon 30 (G>C)) mutation (β0 type) and the mother was heterozygous for HBBc.92+5GNC (IVS I-5 (G>C)) mutation (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. The probability of occurrence of both mutations is very low, because mutations are only 5 base pairs apart on HBB gene. Segregation of compound heterozygosity has occurred twice in this family. Along with the present case, we will share our experience of analyzing 21 unrelated families (trios samples) for detection of β-thalassemia using whole gene sequencing and RT-PCR assays. We will share few interesting case studies like co-inheritance of sickle cell anemia and β-thalassemia traits, compound heterozygosity of beta thalassemia major and normal in the case of twin pregnancy. Prenatal diagnosis helps the parents to know the thalassemic status of the fetus in the first trimester screening.