Thalassemia occurs due to which mutations -a) Missenseb) Splicingc) Transitiond) Frame-shifte) Truncation

Thalassemia syndrome Adult hemoglobin is a tetramer, composed of two α globin chains and two β globin chains. Thalassemia is an inherited autosomal recessive disorder. In thalassemia, the genetic defect results in reduced β synthesis of one of the globin chains of hemoglobin. β-Thalassemia is caused by deficient synthesis of β-chain with normal β-chain synthesis. α-thalassemia is caused by deficient synthesis of α-chain with normal β-chain synthesis. Molecular defect in pathogensis of thalassemia. A. β-Thalassemia Most common type of genetic abnormality in β-thalassemia is point mutation i.e., nonsense. Some may also occur due to deletion or insertion i.e., frame shift mutations. Defect may occur at different steps of β-chain synthesis. (i) Splicing mutations Mutations leading to aberrant splicing are the most common cause of β-thalassemia. (ii) Chain terminator mutations This cause premature termination of mRNA translation. (iii) Promoter region mutations This results in transcription defect. B. α-Thalassemia The most common cause of reduced a-chain synthesis is deletion of α-globin genes. Rarely nonsense mutation may also cause α-thalassemia.