22september 2011, GLT medical College Kolkata88, India..............under Pathology Dept!!!!!!!!1Dr.S.K.Mandal.........chief speakers aVIK bASU, Chirantan Mnadal, Urmimala Bhattacharya, Soumaditya Banerjee!!!!!!!!!

1. THALASSEMIA Burden of the disease And Molecular Pathogenesis By-Urmimala Bhattacharjee (5th Semester) Moderator- Dr Santosh kr Mondal (Associate Professor) Department of Pathology, Medical College, Kolkata.

2. Group of congenital anaemias. Deficient synthesis of one or more globin subunits of normal human hemoglobin According to the chain whose synthesis is impaired, the thalassemias are called α-,β-,γ-,δ-,δβ- or εγδβ- thalassemias.

3. Geographic Distribution Found in high frequency in a broad belt extending from the Mediterranean basin, the Middle East, Indian Subcontinent, Burma, South-east Asia and the islands of the Pacific.

4. THALASSEMIA BELT

5. World-wide 15 million people have clinically apparent thalassemia disorders. There are 240 million carriers of β-thalassemia in the world. In India, 30 million people are β-thalassemia carrier with a mean prevalence of 3.3%. (INDIAN PEDIATRICS, Vol. 44, September 17, 2007, page 647)

6. Every year 100,000 children with thalassemia major are born world over, of which 10000 are born in India. (INDIAN PEDIATRICS, Vol. 44, September 17, 2007, page 647)

7. Carrier rate for β-thalassemia varies from 1-3% in South India to 3-15% in North India. Higher carrier rate is especially noticed in the tribal population all over India. (INDIAN PEDIATRICS, Vol. 44, September 17, 2007, page 647)

8. in tribal population

9. What about West Bengal? Thalassemia trait prevalent in the population of the state in the magnitude of 11.25%. Prevalence among close relatives of cases is 55.26%. Prevalence among scheduled tribes and Muslims is predominantly more. (JIMA, 2006 Jan;104(1):11-5. Prevalence of thalassaemia trait in the state of West Bengal, Sur D, Mukhopadhyay SP. Source- National Institute of Cholera and Enteric Diseases, Kolkata 700010.)

10. General population has a prevalence of 3.6% (males) and 5.95% in antenatal mothers. High prevalence rate is associated with illiterates (19.23%) than literates (5.55%). Highest prevalence rate 20.47% is associated with age group of 0-9 years. (JIMA, 2006 Jan;104(1):11-5. Prevalence of thalassaemia trait in the state of West Bengal, Sur D, Mukhopadhyay SP. Source- National Institute of Cholera and Enteric Diseases, Kolkata 700010.)

11. Molecular Pathogenesis Of Thalassemia.

12. Mutations causing α-thalassemia Deletion α-thalassemia Non-deletion α-thalassemia.

14. -α3.7 kb(rightward deletion)

15. -α3.5kb

16. α[α]5.3

18. -[α]20.5

20. Hb Heraklion (α 137 ProS0) Hb Agrinio (α 29 LeuSPro) 2. Mutation in α-globin gene

21. Mutations causing β-thalassemia Non-deletion β-thalassemia Deletion β-thalassemia

22. Non-deletion β-thalassemia Occurs due to:- Single nucleotide substitution Oligonucleotide insertions/deletions

23. Non-deletion β-thalassemia Mutations altering β-gene transcription Promoter mutation-affecting conserved motifs in 5’ flanking sequence if β gene (TATA box.) 5’-UTR mutation

24. Mutation involving RNA processing Splice junction mutation-Eg.- Mutation at position 5 of IVS-1(G C) Consensus splice mutation Cryptic splice site mutation in introns Cryptic splice mutation in exons Poly A and other 3’-UTR mutation

25. Mutations involving m-RNA translation Initiation codon mutation Nonsense codon mutation Frameshift mutation

26. Deletion β-thalassemia 619-bp deletion removing 3’ end of β-globin gene. This mutation is very common in Punjab and Sind.

30. Thank You