Beschreibung:
<jats:title>Abstract</jats:title><jats:p> <jats:italic>Objectives:</jats:italic> To assess the molecular basis of phenotypic heterogeneity in north Indian patients with thalassemia major (TM). <jats:italic>Methods:</jats:italic> To determine the clinical severity, 130 patients of TM were studied for the age of first presentation and frequency of blood transfusion. The type of beta mutations, <jats:italic>Xmn–</jats:italic>1<jats:sup><jats:bold>G</jats:bold></jats:sup><jats:bold>γ</jats:bold> polymorphism and G6PD Mediterranean mutation was characterized. Analysis of the phenotypic presentation and the genotype was performed. <jats:italic>Results:</jats:italic> Majority (83.8%) presented before 1 year of age (mean 8.8 months). The caste distribution showed 41.6% were Aroras and 32.3% were migrants from Pakistan. IVS1‐5(G→C) was commonest (32.7%) and the common five Indian mutations comprised of 88.4% of alleles. The mean age of presentation with IVS1‐5(G→C), Fr 8/9, (+G) 619‐bp del and IVS1‐1(G→T) homozygosity was 4.3, 6, 3.4 and 9.1 months respectively. <jats:italic>Xmn–</jats:italic>1<jats:sup>G</jats:sup>γ status showed −/− in 66.9%, +/− in 26.1% and +/+ in 6.9% patients. <jats:italic>Xmn</jats:italic>–1<jats:sup>G</jats:sup>γ−/− presented before 1 year of age. The mean age of presentation with +/+ was 18.3 months. Six hemizygous boys and one heterozygous girl with G6PD Mediterranean were found (prevalence 5.3%). Eight patients could be reclassified as thalassemia intermedia on follow up. <jats:italic>Conclusions:</jats:italic> This study showed that majority of TM in north India present before 1 year of age and homozygous 619‐bp deletion presents the earliest. The presence of X<jats:italic>mn‐1</jats:italic><jats:sup><jats:italic>G</jats:italic></jats:sup><jats:italic>γ</jats:italic> polymorphism delays the presentation, is associated with the IVS 1‐1 (G→T) and shows variable improvement with hydroxyurea therapy. Based on the results of genotyping, reevaluation of patients can improve the outcome in a few patients.</jats:p>