Spectrum of Mutations of Beta Thalassemia

  • Khalid Hassan Prof and Head, Department of Pathology, Islamabad Medical & Dental College
  • Memoona Rasheed Research Officer, Islamabad Medical & Dental College
  • Naghmi Asif Prof of Pathology, Islamabad Medical & Dental College
  • Tazeen Anwar Medical Officer, Thalassemia centre, Pakistan Institute of Medical Sciences, Islamabad
  • Mohammad Tahir Medical Officer, Thalassemia centre, Pakistan Institute of Medical Sciences, Islamabad
Keywords: Thalassemia major., Beta Thalassemia, Spectrum, Mutation


Objective: To identify gene mutations known to cause thalassemia major and intermedia amongst patients coming to thalassemia Centre of Pakistan Institute of Medical Sciences(PIMS).
Patients and Methods: Hundred transfusion dependent thalassemia patients were recruited from PIMS. Genome DNA was isolated by using phenol-chloroform method. Allele specific PCR was performed by using primers specific for twelve known disease causing mutations, prevalent in Pakistan. The PCR product was run on 6% polyacrylamide gel electrophoresis and visualized by silver staining technique. Results were recorded and data were entered and analyzed using SPSS version 16.
Results: Total Number of patients included in the study was 100, among them 46% were males and 54% were females. Parenteral consanguinity was seen in 95% cases. Most common homozygous mutations were Fr 8-9 [23(28.7%)], followed by IVSI-5 [17(21.3%)] cases. Compound heterozygous mutations were seen in 20% cases, among them the most common was Fr 8-9/IVS1-5 (5/20 cases), and Fr 8-9/del 619 (3/20 cases). Analysis of type of mutation in different ethnic groups showed that Fr 8-9 was the most common mutation in Punjabis and Pathans seen in 14/63 and 6/28 cases respectively, followed by IVS1-5 seen in 11/63 and 5/28 cases respectively. The most common mutation in Thalassemia major was Fr 8-9 seen in 22 (25%) cases followed by IVS1-5 seen in 15 (17%) cases and Fr 41-42 seen in 10 (11.4%) cases. The number of patients of Thalassemia Intermedia was low in this study (n=12), however among these the commonest mutations were Cap +1, Fr 8-9, IVS1-5 and del 619, presenting as homozygous or compound heterozygous mutations.
Conclusion: Molecular characterization of Thalassemia major and intermedia patients is very essential so that we can set trigger of hemoglobin level accordingly before putting them on regular transfusion. Less frequent transfusion, iron chelation and HU therapy will significantly reduce serum ferritin, liver and spleen size of this group of patients and thus significantly improve their quality of life. 

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