The present study is the first attempt to screen for β-thalassemia-causing mutations by direct sequencing in different districts of West Bengal. The information obtained from the present study may be helpful for thalassemia management and prenatal mutation detection.
We describe a novel C>T substitution at codon 53 of the HBB gene (HBB: c.161C>T). The proband was a transfusion-dependent β-thalassemia major (β-TM) patient. DNA was extracted and subsequently, DNA sequencing was done to detect the mutations on the HBB gene. Capillary zone electrophoresis (CZE) revealed the presence of an unknown peak. She inherited this mutation from her grandmother through her mother. This mutation exists in cis with the common β mutation IVS-I-5 (G>C) (HBB: c.92+5G>C). The proband is homozygous for HBB: c.92+5G>C and needs monthly transfusions. On the other hand, her grandmother, mother and sister all possess this novel mutation cis with the heterozygous HBB: c.92+5G>C. They are carriers not thalassemic. This mutation produces the substitution β53(D4)Ala→Val; HBB: c.161C>T, a new structural hemoglobin (Hb) variant. As this variant was identified in a Bengali family from Paschim Midnapore district of West Bengal, India, it has been designated as Hb Midnapore. This variant has now been reported to the HbVar database.
AimsHbE/β-thalassemia is the prevalent form of severe β-thalassemia in Asian countries. Hydroxyurea (HU) is the most common drug used for the management of sickle-cell anemia but not thalassemia. Here, we aimed to assess clinical HU response among patients with HbE/β-thalassemia with respect to Xmn1 γGglobin polymorphism and elucidate the association between this polymorphism and HU response efficacy.MethodsWe enrolled 49 transfusion-dependent patients with HbE/β-thalassemia. Fetal hemoglobin level was measured using High-performance liquid chromatography (HPLC) and complete blood count was determined pre- and post-HU therapy. Polymerase chain reaction–Restriction fragment length polymorphism (PCR-RFLP) was performed for genotyping Xmn1 γGglobin polymorphism.ResultsA total of 30 (61.22%) patients were found to be responders, whereas the remaining 19 (38.78%) were non-responders. We found 33 patients with heterozygous (C/T) and three with homozygous mutant (T/T) genotype status. We obtained a statistically significant correlation (p < 0.001) between Xmn1 polymorphism and transfusion-free interval. Patients with Xmn1 polymorphism were found to be good responders for HU therapy and showed increased hemoglobin levels.ConclusionsOur findings indicate that HU is a potential drug candidate for thalassemia management, particularly HbE/β-thalassemia. The results hold implications in repurposing HU as an effective and efficient therapy for HbE/β-thalassemia.
Thalassemia is one of the most prevalent inherited blood disorders all over the world. There are some specific hematologic tests and molecular genetic techniques known for diagnosis of thalassemia. Nowadays, various types of drugs are used for the treatment of thalassemia. Hydroxyurea, Hydroxycarbamide, Deferiprone, Deferisirox, Butyrate and its derivatives are some of the most common and well known drugs which are used for increasing the HbF percentage and iron chelation. Pharmacogenomics is the branch of pharmacology that is associated with the influence of genetic variations on the drug response among patients by correlating genetic variations, expression pattern or single-nucleotide polymorphisms with a drug's efficacy or toxicity. With the help of Pharmacogenomics study "personalized medicine" has been explored, in which drugs and drug combinations are optimized for the genetic makeup of each individual.
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