This is a real-world medical entrance exam question, please give the true answer based on the question and selection. Topic name: None, Subject name: Pediatrics
Thalassemia occurs due to which mutations –a)  Missenseb)  Splicingc)  Transitiond)  Frame–shifte)  Truncation 
Select and explain. 
A. c, B. d, C. bd, D. ac
C: bd
Answer: C: bd 
Explanation: 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.