LAUSR

Dear Editor, Thalassemia is an autosomal recessive blood disorder caused by mutations in globin genes. Mutation in α-globin and β-globin gene results in reduced or absent synthesis of alpha and beta globin chain [1]. Thalassemia is common in the Mediterranean region, Africa, South East Asia, and Indian subcontinent [2]. Molecular characterization of β-thal is currently in demand for prevention and better treatment of disease. We have identified and characterized a child from Uttar Pradesh with rare homozygous deletion mutation caused beta thalassemia major. The Sanger sequencing identified 17 nucleotide deletions in beta globin chain of codon 126–131 [HBB:c.380_396 del TGCAGGCTGCCTATCAG] in exon 3 of both the chromosome (Fig. 1a, b). This frame shift mutation generates a TAA stop codon at position 133. A 10-month infant from a Hindu family of Uttar Pradesh was presented with complaint of failure to thrive, fever, jaundice, and pallor presented at OPD of Dept. of Hematology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS) and referred to Genetic Hematology Unit of Medical Genetics Department for evaluation of genetic causes of anemia. High-pressure liquid chromatography (HPLC) was performed using Bio-Rad Variant System (short beta thalassemia program), shown in Table 1. The family members were called for genetic counseling. Written informed consents were obtained from each one of them and blood sample were drawn from 25 members of family for evaluation of HbA2 and HbF levels. The pedigree showed in Fig. 1a. The deletion frame shift mutation of 17 bp causes stop codon (TAA) at position 133 in β globin chain. The truncated β mRNA transcript becomes highly unstable, and thus the unpaired alpha globin chains get precipitated and form Heinz bodies due to interruption in interaction ofα2/β2 dimer formation [3]. This deletion was reported earlier by Waye et al. [4] in heterozygose form in association with Hb E (HBB: c.79G>A) in family originated from India. Later in 2002, Nadkarni et al. [5] and Dehury et al. [3] reported 3 cases of same mutation in carrier state from Madhya Pradesh and four cases of 17 bp deletion with hemoglobin S from Odisha respectively. The above mentioned reports indicate the presence of this mutation either in heterozygous form or in combination with hemoglobin variant (Hb S or HbE) in Indian origin families. In this context, this is the first report which indicates the presence of 17 bp deletion in homozygous state in an Indian subject. We have compared the hematological findings of previously reported patient to present case (Table 2). Our study reveals that the patients with rare mutation presenting with severe clinical manifestations due to homozygous mutation leads to B/B genotype. This clearly indicates the need of redefining the spectrum of rare hemoglobin mutations in Indian subcontinent. * Sarita Agarwal [email protected]