Nitu NigamKing George’s Medical University, India
Title: To govern the pervasiveness of Xmn-1G? gene polymorphism: A significant determinant in children with ?-Thalassemia major and its effect on clinical phenotype and psychological status
Background: Beta-thalassemia is the most widely recognized single gene disorder with >200 mutations. The severity of ?-thalassemia is directly related to imbalance in ?-globlin chain. This imbalance can be reduced by ?-chain production, which combines of with excess ? chain to form fetal Hb (HbF). The increase HbF is genetically determined as well as partiality associated with ?-haplotypes which shows particular microsatellite sequence or the Xmn 1G? gene polymorphism sequence. In this study, we aim to determine the prevalence of Xmn-1 G? gene polymorphism in children with ?-Thalassemia and its effect on clinical phenotype.
Methods: In this prospective observational study, total 101 diagnosed Beta thalassemia children were included from the department of Paediatrics. For screening offive common mutations [IVS I-5 (G?C), -619 bp deletion, IVS I-1 (G?T), Cd 41/42 (-CTTT) and Cd 8/9 (+G)]by ARMS PCR. The polymerase chain reaction–restriction fragment-length polymorphism (PCR–RFLP) was used for genotypingXmn 1 gene polymorphism. The Chi-square test and t- test were used for statistical analysis.
Results: Out of 101 confirmed thalassemia patients, 79 were Thalassemia major, 22 were Thalassemia intermedia. Among the 22 children with Thalassemia Intermedia, 12 were E-beta thalassemia and 6 were S-beta thalassemia and 4 were unknown.Out of 79 children with thalassemia major, a common mutation could be identified in 53 (67.08%). Inwhich IVS I-5 G?C was the commonest ?-thalassemia mutation. The average transfusion (per year) was significantly lower in homozygous mutated TT genotype as compared to homozygous CC and heterozygous CT genotypes. The C and T allele frequencies of Xmn-1G? gene polymorphism were 85 (80.19%) and 21 (19.81%) in common ?-thalassemiamutation
Conclusion: The common mutation could be identified in 61.3% children with beta thalassemia and IVS I-5 G?C was the most prevalent mutation. Among the homozygous mutant TT genotype, the average transfusion frequency was significantly lower as compared to CT and CC genotypes.
Nitu Nigam has received Ph.D (Medical Genetics) from Sanjay Gandhi Institute of Medical Sciences, Lucknow in 2003. She did postdoctoral training in cancer genetics from USA.. An increased genetic risk or a genetic diagnosis can substantially impact medical management as well as the psychological and social well-being of the patient and family. The personal and permanent nature of genetic information raises a range of emotions including guilt, fear, and helplessness. A major research focus of Dr Nigam’s lab is to identify and characterize the molecular players in chromosomal aberrations pathways. For this she conducts the genetic screening of affected families in population and utilize cellular /animal models for testing and validating the hypothesis. Discovery of critical player in genetic disorders (broken, missing, rearranged, or extra chromosomes can diagnose disease and define treatment options. With better understanding of disease producing genes, genetic testing has become a more common place, and diagnosis is extended from not only post natal period to prenatal period but even preconception period.