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THALASSEMIA INTERMEDIA. Data from Dubai Thalassemia Centre . BY: Dr. MOHD SALAH. Chromosome 11 -globin gene. Chromosome 16 -globin gene. Chromosomes. INHERETENCE. An example of inheritance: Marriage between two carriers. Red blood cell. Oxygen from lungs. - PowerPoint PPT Presentation
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Data from Dubai Thalassemia Centre
Chromosome 11-globin gene
Chromosome 16 -globin gene
An example of inheritance:Marriage between two carriers
Red blood cell Oxygen from
lungsOxygen released to tissue cells
Oxygen boded with hemoglobin molecules
Hemoglobin molecules
1. 1. Homozygous or compound heterozygous state for thalassemia
a) Inheritance of mild thalassemia alleles
b) Co-inheritance of thalassemiac) Increased Hb F response
Xmn1 –polymorphism promoter mutations Trans-acting HPFH genetic
determinants
2. 2. Heterozygous state for thalassemiaa) Co-inheritance of extra globin genes
()
b) Dominantly inherited thalassemia(Hyperunstable chainvariants)
3. Compound heterozygous for thalassemia and chain variants e.g. Hb E
4. Compound heterozygotes for thalassemia and HPFH .
-Thalassaemia genotypes of parents HbF values in parents Co-inheritance of thalassemia Age at presentation Level of Hb at presentation Level of Hb A
All patients had:Serial FBCsHb Electrophoresis (HPLC) &/ or IEFMolecular characterization of alphagenes ( Deletional and non-deletional) Beta genes mutations &Xmn1Clinical monitoring of any possiblecomplication
HbA: Decreased HbF: Inc(80-90 %) HbA2: Variable
HbA: Decreased(>20%) HbF: Inc(70-80 %) HbA2: N or Increased
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.
509
420
44 45
0
100
200
300
400
500
600
Total BTM BTI BMT
No of pts
82.52%
8.64%
8.84%
44%
33%
23%
severe mutation mild mutation mixed
2515
62.5
37.5
0
10
20
30
40
50
60
70
no. of pts %
male female
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
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)
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)/ 1= -25 bp del / CD 27 (G-T) 25 bp del / CD 27 (G-T)
14
4
6
10
6
02468
101214
No. of pts
Homozygous severe Hetero severe Homo mildHetero mild/severe Hetero mild/mild
9, 47%
4, 21%
6, 32%HomozygousWith severeWith mild
IVS 1-5(GC) =19
-Thal. Status
18 severe - mutation
8 normal - thal
4 heterozygous -thal 3.7
6 homozygous -thal 3.7
13 13
5
9
0
2
4
6
8
10
12
14
Never tx Rarely tx Freq. tx Planned tx
Total Severe mut. Mild mut.
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/P 2- P/ - ve
13
8
5
0
2
4
6
8
10
12
14
No of pts
total mild mutation severe mut.
2 PTS
SEVERE MUTATION N-geneDeletional & nondeletional N- Xmn1
2 PTSSEVERE MUTATION 1 a-GENE DELETION Xmn1-p/p
1-Pt a- Thal. Trait
0 0.5 1 1.5 2 2.5 3
Thal. Features
pregnancy
path. fracture
Delayed puberty
Multifactorial
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.
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.