Molecular epidemiology of β-thalassemia in pakistan: Far reaching implications

Abstract

BACKGROUND:β -Thalassaemia, an autosomal recessive hemoglobinopathy, is one of the commonest genetically transmitted disorders throughout the world. Collective measures including carrier identification, genetic counseling and prenatal diagnosis are required for preventing β-thalassemia.Aim:To achieve this objective, Identification of the spectrum of genetic mutations, especially for various ethnic backgrounds in Pakistan. Therefore, we designed a cross sectional prospective study to identify the frequency of various gene mutations in different ethnic groups of Pakistan.MATERIALS AND METHODS:Over a 5-year period, DNA from 648 blood samples {including specimens of chorionic villus sampling (CVS)} were analyzed for the twelve most common β-thalassemia mutations found in the Pakistani population by a Multiplex amplification refractory mutation system (ARMS). Each sample was analyzed for the mutation as well as the normal gene, appropriate with negative and positive controls, and reagent blanks.RESULTS:Out of 648 samples mutations were identified in 640 (98.75%) samples by multiplex ARMS. 8 common β-thalassemia mutations were identified in 8 different ethnic groups accounting for 93.9% of the β-thalasemia alleles.CONCLUSIONS:Based on the outcome of this study a cost effective proposal is formulated for detection of β-thalassemia mutations.

Serum Ferritin;

“…According to the literature anticipated population proportion in Pakistan was 5-7%. 18 Using the Epiinfo version 6 / WHO software; the calculated sample size was; n = 156 by considering:…”

An Insight in Understanding the Symptomatology of β-Thalassaemia Major - II

“…on intracellular anti-oxidant levels, metabolic pathways, handling of trace elements required for enzymes in different metabolic pathways, oxygen binding and dissociation from haemoglobin-F are not entirely known. Our group has previously reported interesting results of proteomics, metallomics, metabolomics and genomics in β-thalassemia patients with and without the institution of HU [9][10][11][12][13]. Primary and secondary genetic modifiers, like beta globin gene mutations and presence or absence of XMN-1, HSB1L-MYB, and BCL-11A polymorphisms, have been found to significantly influence the response of HU in improving haemoglobin levels in beta thalassemia patients [14].…”

Beta thalassemia - a review

“…6 An estimated 5000-9000 children with beta thalassemia are born per year in Pakistan and the estimated carrier rate is 5 to 7%, with 9.8 million carriers in the total population. 7 Google search using term " beta thalassemia in Nepal" didn't show any published data that would indicate the burden of beta thalassemia in Nepal but unpublished hospital records of Tribhuwan University Teaching Hospital shows beta thalassemia more prevalent in the tharu community.…”