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

Thalassemia syndrome                                                                                                   Adult hemoglobin is a tetramer, composed of two a globin chains and two β globin chains. Thalassemia is an inherited autosomal recessive disorder. In Thalassemia, the gentic defect results in reduced synthesis of one of the globin chains of hemoglobin. β- Thalassemia is caused by deficient synthesis of β-chain with normal α-chain synthesis. α- thalassemia is caused by deficient synthesis of α-chain with normal (β-chain synthesis. Molecular defect in pathogenesis of thalassemia. A) β-thalassemia Most common type of genetic abnormality in (-thalassemia is point mutation, i.e. nonsense. Some may also. occur due to deletion or insertion i.e. framshift 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. 10 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 α-chain synthesis is the deletion of α-globin genes. Rarely nonsense mutation may also cause α-thalassemia.