This document discusses thalassemias, which are a group of genetic blood disorders caused by deficient production of hemoglobin subunits. It notes that thalassemias are most common in a belt extending from the Mediterranean to Southeast Asia. Specifically in India, 30 million people are beta thalassemia carriers, with higher rates in North India and tribal populations. The document also discusses prevalence of the trait in West Bengal, where it affects 11.25% of the population and is more common in scheduled tribes, Muslims, illiterate groups and young children. It outlines different types of alpha and beta thalassemia mutations including deletions and non-deletions.

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.)

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

13. Deletion α-thalassemia
α + type
• Single α globin gene
deletion.
 -α4.2 kb (leftward deletion)
 -α3.7 kb(rightward deletion)
 -α3.5kb
 α[α]5.3
 Region containing α1 gene.
α 0 type
• Deletion of both α1 and α2
globin gene.
 -[α]5.2
 -[α]20.5
 HS40 deletion alone
keeping α1 and α2 sites
intact.

14. Non-deletion α-thalassemia
• Hb Constant Spring(α 142 TAASCAA, StopSGlu)
• Hb Icaria (α 142 Lys)
• Hb Koya Dora (α 142 Ser)
• Hb Seal Rock (α 142 Glu)
• Hb Paksé (α 142 Tyr).
1.Due to modification of stop codon.
(Continued…)

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

16. Mutations causing β-thalassemia
• Non-deletion β-thalassemia
• Deletion β-thalassemia

17. Non-deletion β-thalassemia
• Occurs due to:-
1. Single nucleotide substitution
2. Oligonucleotide insertions/deletions

18. Non-deletion β-thalassemia
• Mutations altering β-gene transcription
1. Promoter mutation-affecting conserved
motifs in 5’ flanking sequence if β gene (TATA
box.)
2. 5’-UTR mutation

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

20. • Mutations involving m-RNA translation
1. Initiation codon mutation
2. Nonsense codon mutation
3. Frameshift mutation

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