Thalassemia is one of the most common genetic blood disorders worldwide. The carrier rate of β thalassemia in Pakistan is found to be around 5-7%, rendering it a major health concern. Approximately 5000 children are diagnosed with thalassemia major every year in Pakistan due to consanguineous marriages. More than 200 causative molecular defects have been identified in β-globin genes. About 20 mutations account for 90% of the abnormal β-genes. Clinical severity of β-thalassemia is modified by different factors. The important ones include the type of disease causing mutation and the ability to produce α and γ globin chains. A better understanding of these ameliorating factors may have a significant impact on disease management.


1. To re-assess diagnoses among local multi-transfused thalassemia syndrome patients.

2. To determine frequency of various genetic determinants of milder phenotypes of thalassemia among study patients.


Transfusion dependent thalassemia patients, upto 15 years age, were enrolled from Fatimid Foundation, Peshawar Pakistan. A comprehensive questionnaire encompassing demographic and clinical data was filled out for each patient. Genetic analyses for 2 alpha (α) and 13 prevalent beta (β) gene mutations and for polymorphisms at Xmn1-HBG2 and BCL11A were carried out on blood samples of the patients at National Institute of Blood Diseases, Karachi Pakistan. The data collected was analysed at Khyber Medical University (KMU) Peshawar Pakistan.


A total of 54 transfusion dependent thalassemia patients were enrolled into the study. Homozygous or compound heterozygous combinations of β-globin gene mutations were identified in all the study patients. Eleven patients were found to have a co-existing heterozygous α (3.7kb) deletion, two patients had Xmn1-HBG2 polymorphism and 38 had BCL11A polymorphism. Homozygous Fr 8-9 was the most frequent mutation, found in 19 (35.2%) patients. Only 13 patients were found to have isolated β-globin gene mutations. In total, 46 (85.2%) study patients were identified to have an ameliorating genetic factor (a co-existing α-globin gene mutation, an Xmn1-HBG2 polymorphism or a BCL11A polymorphism) besides the main β-globin gene mutation.


It was concluded that co-existing genetic ameliorating factors are frequently found in transfusion dependent β-thalassemia patients of Peshawar District. These factors impart a milder phenotype to an otherwise severe disease. It is hence suggested that β-thalassemia patients from District Peshawar be screened for these factors and due consideration be paid by the physician in devising management plans.

Key Words

Thalassemia, Genetic modifier in thalassemia, Transfusion dependent Anaemia, Xmn1 polymorphism


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.

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