1. Data from Dubai Thalassemia Centre

2. Chromosome 11  -globin gene Chromosome 16  -globin gene

3. An example of inheritance: Marriage between two carriers

4. Red blood cell Oxygen from lungs Oxygen released to tissue cells Oxygen boded with hemoglobin molecules Hemoglobin molecules

5. 1. 1. Homozygous or compound heterozygous state for  thalassemia a) a) Inheritance of mild  thalassemia alleles b) b) Co-inheritance of  thalassemia c) c) Increased Hb F response   Xmn1 –polymorphism    promoter mutations   Trans-acting HPFH genetic determinants

6. 2. 2. Heterozygous state for  thalassemia a) Co-inheritance of extra  globin genes (  ) b) Dominantly inherited  thalassemia (Hyperunstable  chain  variants) 3. Compound heterozygous for  thalassemia and  chain variants e.g. Hb E 4. Compound heterozygotes for  thalassemia and HPFH.

7.  -Thalassaemia genotypes of parents HbF values in parents Co-inheritance of  thalassemia Age at presentation Level of Hb at presentation Level of Hb A

9. All patients had: Serial FBCs Hb Electrophoresis (HPLC) &/ or IEF Molecular characterization of alpha genes ( Deletional and non-deletional) Beta genes mutations &Xmn1 Clinical monitoring of any possible complication

10.       HbA: Decreased HbF: Inc(80-90 %) HbA 2 : Variable       HbA: Decreased(>20%) HbF: Inc(70-80 %) HbA 2 : N or Increased

11.   The mean age is 11 (3-33) yrs,   Non-deletional alpha-gene mutation was normal in all our patients.   Most of pts have mild to moderate thalassemic features.   Average hemoglobin level : 8.5 g/dl.   40% of patients had infrequent hemoglobin drop needed blood transfusion.

12. 82.52% 8.64%8.84%

15. 9 = IVS 1 - 5 (G-C) / IVS 1 - 5 (G-C) 4 = IVS 1 - 5 (G-C) / - 25 bp del 3 = IVS 1 - 1(G-C) / IVS 1 – 1(G - C) 1 = IVS 1 - 1 (G-T) / IVS 1 - 1 (G - T) 1 = -25 bp del / -25 bp del

16. 2 = CD 26 (G-A) / Milder mutation 2 = IVS 11–1 (G-C) / IVS 11 – 1 1 = IVS 1-6 (T-C) / IVS 1-6 (T-C) 1 = CD 27 (G-T) / CD 39 (G-T) 1 = CD 26 (G-A) / IVS 1 – 130 (G-C) 2 = VS 1-6 (T-C) / mild 2 = IVS 1-6(T-C) / IVS II-848(C-A) 2 = Cd 8 (-AA) / Cd 8 (-AA)

17. 2 = IVS 1 - 5 (G-C) / - 88 (C-A) 3 = IVS 1 - 5 (G-C) / Poly A 2 = IVS 1– 5 (G-C) / CD 26 (G-A) 1 = IVS 1 – 5 (G-C)/ 25 bp del / CD 27 (G-T) 1 = -25 bp del / CD 27 (G-T)

19. IVS 1-5(G  C) =19

20.  -Thal. Status 18 severe  - mutation 8 normal  - thal 4 heterozygous  -thal 3.7 6 homozygous  -thal 3.7

22. 4/20 (20%) patients received blood transfusion rarely 4/4 (100%) are homozygous positive for XmnI, 2/4 (50%) are heterozygous for –3.7 alpha-gene mutation (alpha-thalassemia trait) Xmn1 5-P/P2- P/ - ve

24. 2 PTS SEVERE MUTATION N-  gene Deletional & nondeletional N- Xmn1 2 PTS SEVERE MUTATION 1 a-GENE DELETION Xmn1-p/p 1-Pta- Thal. Trait

29. Among the known factors affecting the phenotypic severity in our pts.: Type of Beta mutation. The presence of alpha-gene defect. XmnI mutation (homozygous and hetero) would ameliorate the clinical course. Two of our patients have severe mutation with normal a-thal and normal Xmn1 Further studies still needed to specify other factors.

30. Erol Baysal, PhD Aref Chehal, MD Maisam Bakir,MD Essam Dohair, MD Lab. Technicians Nursing Staff Abdulla Alkhayat.MD Al Wasl Hospital, Genetic and Thalassemia Center, Dubai, UAE.