-
THALASSEMIA
Thalassemia is the number one heritable disease in India. It is an autosomal recessive blood disorder characterized by reduced or absent synthesis of globin chains. Carrier frequency for haemoglobinopathies is nearly 3-15 % in general population. As a result most silent carrier state of the Thalssemia couple may give birth to Thalassemic child without knowing their carrier state.
Thalassemic patients display a wide range of phenotypic diversity, ranging from severe transfusion dependency to non-transfusion dependent. The inheritance of mutation in the HBB or HBA genes control the clinical expression of the disease. Several ‘modifier loci known to influence the heterogeneity in the clinical presentation, ranging from severe to silent types. Many primary or secondary modifier loci may influence the phenotype presentations. There is a need to address comprehensive genetic diagnostic method and also fishing the unknown loci for phenotype heterogeneity.
​
i) Currently, Coordinator of the multicentric project on Thalssasemia genomics, funded by DBT – Human Genetics task force, participated by PGIMER, Chandigarh, University of Burdwan, also with Institute of Child Health ICH), Kolkata and Burdwan Medical College, Burdwan, for the development of genetic diagnostic method of Thalassemia in North Indian and Eastern Indian population and searching of modifier loci .
ii) Technology for field-based thalassemia carrier detection kit
Thalassemia is the major inherited disorder in India. Based on the origin of the different ethnic group, residing in different states of India, there is 3- 17% carrier frequency in general population. As a result, it has been reported that there would be 32,400 babies with a thalassemia syndrome born each year. Unfortunately, among them majority of the children may not able to survive more than10 -12 years for repeated blood transfusion. One of the obstructions for the thalassemia prevention is the non-availability of any simple field-based method or kit for carrier screening. Only available method is the HPLC based method, which limits the access of the large population of India to tertiary laboratory for carrier detection. Under the funding support from BIRAC, DBT a field based simple carrier screening kit has been developed. Accordingly, patent has been filed recently to the Indian patent office.
iii) Mutation profile and Genetic Diagnostic procedure for thalassemia
Last several years, our group is working for the cataloguing of the different mutational profile in the Bengali as well as in Indian population. We have showed that only two mutation IVS-1-5 (G>C) and CD 26 (G>A) are very common in Bengali population (Papers already published and PhD work done). It has also been found HbE is very prevalent in Eastern Indian population and rare in North Indian population. Our group also showed the role of alpha globin gene mutation in Beta Thalassemia (Paper archived and under publication). Thus, actual genetic diagnosis for thalassemia need multi-level approach. Accordingly, currently we are running a multicentric project for revised genetic diagnostic protocol for thalassemia (Project was previously supported by WB-DST and now by DBT GoI).
iv) Modifier Gene for Thalassemia phenotype heterogeneity
It has been observed that there is remarkable phenotype heterogeneity among the thalassemia patients having same HBB genotype. In spite of having same HBB genotype like E – Beta thalassemia, group of patients need blood transfusion regularly (TDT) on the other hand, other group of patents do not need transfusion regularly (NTDT). We are currently doing whole exome sequencing (WES) to decipher any modifier gene other than globin gene that may be responsible for transfusion dependent thalassemia. Recently we have completed a family-based study and figure out candidate genes through WES that are responsible for making severe phenotype but with same beta globin genotype (Paper Under publication). We are still undertaking WES work for the more recruited patients of the aforesaid two groups (Project is supported by DBT GoI).
​
Important Findings:
we have discovered 14 different mutations that are responsible for pathological mutations in Bengali population. We have discovered novel mutation IVSI-129 (A>C) for Thlassemia Major (HbVar ID 2946), and novel hemoglobin – “Hb Midnapore [CD 53 (C>T)]’ and included in the world HbVar Database (Human Hemoglobin Variants and Thalassemias)
​
Fig. Screening of β-thalassemia mutations by Sanger sequencing method after amplification of 800 bp fragments of human beta globin gene. Arrows within the chromatograms showing the respective mutations in the HBB gene (Panja et
and Anupam Basu ).
