Establishing Mutational Spectrum of Beta Thalassemia by Molecular Screening in a Low Resource Setting – Implications in Counseling and Prevention
[1]
Gayatri Rangarajan Iyer, Department of Genetics & Molecular Medicine, Kamineni Hospitals, LB Nagar, Hyderabad, India.
[2]
Aruna Priya Kamireddy, Department of Genetics & Molecular Medicine, Kamineni Hospitals, LB Nagar, Hyderabad, India.
[3]
Saroja Kondaveeti, Thalassemia & Sickle Cell Society (TSCS), Chatta Bazar, Purani Haveli, Hyderabad, India.
[4]
Suman Jain, Thalassemia & Sickle Cell Society (TSCS), Chatta Bazar, Purani Haveli, Hyderabad, India.
[5]
Qurratulain Hasan, Department of Genetics & Molecular Medicine, Kamineni Hospitals, LB Nagar, Hyderabad, India.
Introduction: The incidence of hemoglobinopathies is alarming in India with 1 in 14 individuals estimated to be carriers most of them for Beta-Thalassemia. Lifelong transfusion and associated medical treatment imposes an emotional and financial burden on families and on the healthcare system. To prevent this, biochemical/molecular screening with genetic counseling is essential for a planned public health programme. Methods: The present study assessed the clinical, demographic and molecular analysis details of a subset of patients from the 2054 registered at Thalassemia & Sickle Cell Society (TSCS), Hyderabad, India. Patients (N = 600) were interviewed during group and individual genetic counselling sessions in two phases, 2014 and 2017, about the condition, their molecular analysis report. Zygosity, frequency and types of sequence variations were recorded. Results: The patients referred to TSCS, (an NGO catering to a low socio-economic group of thalassemics) were from 21 districts of the 2 states, Telangana and Andhra Pradesh, India. About 59.19% patients were diagnosed by 6 months of age and 93.42% by 2nd year of life. The gender ratio was 1:1.24 with more skewed in the group opting for molecular testing. Only 12% of the cases had molecular testing in 2014, whereas it increased to 40% in 2017, this was due to the introduction of the state government programme (2015) which mandated molecular analysis of HBB gene prior to availing free transfusions. The molecular data showed 70.93% of the patients were homozygous, whereas 27.09% were compound heterozygous and 1.97% were surprisingly only heterozygous for the sequence variations. IVS 1-5 (G-C) was the most common mutation (73.15%), followed by FS codon 15 (TGG-TAG), which was seen in 13.05% of the cases. The other 25 mutations observed included five unreported from India and two novel mutations. Conclusion and Guidelines: Results indicate that instead of whole HBB gene sequencing, targeted IVS 1-5 (G-C) could be analysed as first line screening in this Southern region of India which would reduce the cost of molecular testing by 80%. Other state governments should follow the guidelines of Telangana state model and make molecular analysis mandatory. National Public health policy guidelines should implement biochemical screening programme linked to Aadhar card which is a unique identifying number for citizens. Molecular testing with genetic counseling for patients/carriers in the reproductive age (18-40 years) will not only provide molecular diagnosis but also facilitate extended family screening, premarital counseling and prenatal diagnosis eventually decreasing the burden of this disease.
Beta Thalassemia, Mass Screening, Public Health, Genetic Counseling, Hemoglobinopathies
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