Abstract for presentation at 11th International Congress of Human Genetics

Molecular basis of Thalassemia Intermedia in North Indians

  • Dr Reena Das, Haematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
  • Dr Gurjeewan Garewal, Haematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
  • Dr R K Marwaha, Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    • The prevalence of β thalassemia trait (βTT) is 3.5% in the general population of North India. The clinical presentation of Thalassemia intermedia (TI) is variable ranging from near transfusion dependence to a very mild disorder presenting in adulthood. This heterogeneity in phenotype is matched by an equal heterogeneity in genotype. The patients of TI at the genetic level are most commonly homozygous or compound heterozygous for β-thalassemia, having both β-globin loci affected. Less commonly, only a single β-gene is mutated, the other being completely normal.
    We analyzed the spectrum of mutations in 805 beta thalassemia alleles by PCR-ARMS (Tab. 1) for fourteen mutations. Differences were observed in the frequency of the Cap +1 mutation (found exclusively in Asian Indians) and -88 M (C-T) between the alleles of TI and thalassemia major (TM). The -88 M (C-T) is observed in a particular caste, the Jat Sikhs.
    Tab. 1: Spectrum of beta thalassemia alleles in TI and TM
    Amongst the TI homozygosity for IVS 1,1 (G-T) was seen in 20% of cases and all these cases were associated with the Gγ Xmn-1 polymorphism that is known to increase the γ-globin chain output. Homozygosity for -88 M (C-T) was noted in 15% of TI. The prevalence of α+-thalassemia and triplicated α-genes in this region and its interaction with β-thalassemia also plays a role in influencing the phenotype. In a study by us, we have shown that nearly 13% of β-thalassemia trait had concomitantly inherited α+-thalassemia and 3% had triplicated α-genes (Trehan et al, 2001).
    Mutations TI % TM % Total %
    IVS 1,5 (G-C) 29 14 170 28.4 199 24.7
    619 bp del 10 4.83 113 18.9 123 15.3
    IVS 1,1 (G-T) 65 31.4 50 8.36 115 14.3
    Fr 8/9 (+G) 23 11.1 104 17.4 127 15.8
    Fr 41/42 (-TTCT)14 6.76 77 12.9 91 11.3
    -88 M (C-T) 41 19.8 18 3.01 59 7.33
    Cap +1 (A-C) 15 7.25 14 2.34 29 3.6
    -88 (C-A) 1 0.48 0 0 1 0.12
    IVS 1,1 (G-A) 0 0 2 0.33 2 0.25
    Codon 15 (G-A) 2 0.97 11 1.84 13 1.61
    Codon 16 (-C) 1 0.48 16 2.68 17 2.11
    Codon 30 (G-A) 2 0.97 1 0.17 3 0.37
    Codon 5 (-CT) 0 0 5 0.84 5 0.62
    Fr 47/48 (+ATCT)0 0 5 0.84 5 0.62
    Rare 4 1.9 12 2.0 10 1.24
    207 598 805

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