12. Common mutations in β thalassemia
Racial Group Description
Mediterranean IVS-1, position 110 (G â A)
Codon 39, nonsense (CAG â TAG)
IVS-1, position 1 (G â A)
IVS-2, position 745 (C â G)
IVS-1, position 6 (T â C)
IVS-2, position 1 (G â A)
Black -34 (A â G)
-88, (C â T)
Poly(A), (AATAAA â AACAAA)
Southeast Asian Codons 41/42, frameshift (-CTTT)
IVS-2, position 654 (C â T)
-28 (A â T)
Asian Indian IVS-1, position 5 (G â C)
619-bp deletion
Codons 8/9, frameshift (++G)
Codons 41/42, frameshift (âCTTT)
IVS-1, position 1 (G â T)
17. Thalassemia Syndromes
⢠Occurs because of diversity & high prevalence of Hb mutations
Simultaneous
inheritance of 2 diff
thal mutations
Coinheritance of
thal with structural
Hb variants
20. NTDT
ďNon transfusion-dependent thalassemia (NTDT) is a group of
thalassemias for which patients do not require regular red cell
transfusions for survival
ďThey may require occasional or even frequent transfusions in certain
clinical settings & for defined period such as for growth failure,
pregnancy, infections
ďThere are 3 NTDTs
ďβ-Thalassemia intermedia
ďMild/moderate Haemoglobin E β-thalassemia
ďÎą thalassemia intermedia (HbH disease)
2 Seperate entity with similar transfusion requirement
ďHaemoglobin S β-thalassemia
ďHaemoglobin C β thalassemia
22. Genetic & environmental modifiers of
phenotype
⢠β-Thalassemia intermedia
â˘Broad diversity of mutations
â˘Variable degree of Îą/β chain imbalance
Primary
modifiers
â˘Coinheritance of Îą thal
â˘Genes modifying Îł chain production
Secondary
modifiers
â˘Polymorphisms affecting specific complication
of disease (iron absorption,bili metabolism,
bone metabolism, cardiovascular disease)
Tertiary
modifiers
23. Hb E /β thalassemia
â˘Type of β thal mutation
Primary
modifiers
â˘Coinheritance of Îą thal
â˘Genes modifying Îł chain production
Secondary
modifiers
â˘Inherited variability in function of gene for UDPG transferase
â˘Advancing age affecting EPO productin in response to anemia
â˘P.Vivax infection
Tertiary
modifiers
25. Îą thalassemia
⢠Limited studies
⢠Different sizes of ι globin gene
deletions
⢠7 forms of non deletional HbH
disease
Primary
modifiers
⢠Co-inheritance of β thal trait
⢠Role of ι Hb stabilising protein
Secondary
modifiers
28. Regulators of hepcidin production
ďGrowth differentiation factor-15
ďTwisted gastrulation factor-1
ďHypoxia inducible transcription factors
ďTransmembrane protease serine-6 (TMPRSS6)
29. Characteristics of iron overload in NTDT
⢠Low ferritin level d/t increased labile plasma iron pool
⢠Liver iron 5mg/gm dry wt is considerable morbidity risk factor
⢠Cardiac iron overload not a major concern