Hemoglobinopathies are the most commonly inherited genetic disorders in India. Certain communities in India have a high predisposition to beta-thalassemia. To offer prenatal diagnosis and to prevent the birth of an affected child, mutation testing in clinically diagnosed beta-thalassemia patients/carriers is a prerequisite. Over a period of 4 years, we have conducted DNA analysis in 385 carriers for 15 beta-thalassemia mutations, HbD, HbE, and HbS. Using reverse dot blot (RDB) and amplification refractory mutation system (ARMS), we have been able to identify mutations in 381 of 385 thalassemia chromosomes. The study included the analysis of five common mutations found in Asian Indians, namely IVS1-5 (G-C), 619-bp deletion, IVS1-1 (G-T), and the frameshifts at CD8/9(+G) and CD41/42(-CTTT). The occurrence of these five mutations was seen in 299 (91.2%) carriers referred to us, the percentage of mutations varying between 4.0 and 68.9%. We also found Cd16 (-C) in 2.1%, CD30 (G-C) in 1.5%, and CD 15(G-A) in 0.6%; these are considered common mutations in the Indian population, as well. The beta-thalassemia anomaly in 4 (0.6%) carriers remained uncharacterized by RDB and ARMS analysis. During delineation of the mutations in uncharacterized carriers by single-stranded conformational polymorphism (SSCP) and sequencing analysis, we have also been able to identify two unusual mutations, one involving an initiation codon and the second involving a novel 8-bp deletion, in Indian families of Uttar Pradesh origin.
Background and Aims:
Hemoglobinopathies and thalassemias are the commonest single gene disorders in India. In Terai region of India, Hemoglobinopathies and thalassemias are the most common in the Tharu community. Therefore, in this study, we aim to evaluate the Hb variant analysis of hemoglobinopathies and thalassemias in a Tharu population in Lakhimpur Kheri Districts of Uttar Pradesh, India.
Materials and Methods:
Total 493 individuals were recruited in this study. The demographic details and blood samples were collected from different location at Kheri district during mega health camp. Hb variant analysis was performed by high performance liquid chromatography (HPLC) system beta thalassemia short program in BIO-RAD VARIANT.
Results:
Out of 493, 108 (21.9%) individual suffers with abnormal haemoglobinopathies. In which β-thalassemia trait is the commonest haemoglobinopathy (12.98%), followed by HbE trait (7.50%), and compound heterozygous HbS/β-Thalassemia trait (1.42%) in overall population. The HbF was significantly greater in HbS heterozygous (1.45 ± 1.41), whereas mean HbA2 was significantly greater in β-Thalassemia trait (5.17 ± 1.36).
Conclusion:
The high incidence of hemoglobinopathies and thalassemias were observed in Tharu community in Lakhimpur Kheri districts of Uttar Pradesh, Indian.
The β-thalassemia is a hereditary blood disorders, characterized by reduced or absent synthesis of the hemoglobin beta chain that cause microcytic hypochromic anemia. An early diagnosis, economical test, awareness programs and prenatal screening will be a milestone for the eradication of this genetic disorder and to reduce burden of the health sector of a country subsequently the economics. Initially, the diagnosis of β-thalassemia depends on the hematological tests with red cell indices that disclosed the microcytic hypochromic anemia.Hemoglobin analysis shows the abnormal peripheral blood smear with nucleated red blood cells, and reduced amounts of hemoglobin A (HbA). In severe anemia, the hemoglobin analysis by HPLC reveals decreased quantities of HbA and increased the level of hemoglobin F (HbF).The decrease level of MCV and MCH are also associated with β-thalassemia. There are various different molecular techniques such as ARMS PCR, allele-specific PCR, Gap PCR, denaturing gradient gel electrophoresis, reverse dot blotting, DGGE, SSCP, HRM, MLPA, sequencing technology and microarray available to identify the globin chain gene mutations. These molecular techniques can be clustered for detection by mutation types and alteration in gene sequences.
BACKGROUND:
Himachal Pradesh is a hill state in North India in the Western Himalayas. β-thalassemia is a genetic disorder of hemoglobin inherited in an autosomal recessive manner that results in defective globin production leading to the early destruction of red blood cells. β-thalassemia has long been neglected in Himachal Pradesh due to popular belief that it runs along “Lahore-Gujarat-Punjab” belt in India. Therefore, there is no β-thalassemia testing facility currently in the state.
METHODS:
To estimate the prevalence of β-thalassemia carriers, we calculated the sample size based on probability proportional to size self-weighing design. In each of 20 selected colleges, 111 students having an age of 18–25 were tested for high-performance liquid chromatography (HPLC) and complete blood count. Some were further tested for the mutations. We computed sensitivity, specificity, positive predictive value (PPV) and negative predictive value, and receiver operating characteristic curve for mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) red cell parameters.
RESULTS:
Of the 2220 students, 57 were found to be β-thalassemia carrier by HPLC. The overall prevalence rate was 2.6% which translates to probable 180,000 β-thalassemia carriers in Himachal Pradesh. Six districts bordering highly endemic Punjab had a higher prevalence. Hemoglobin D-Punjab, Heterozygous-Iran Trait, and raised fetal hemoglobin were found. Thalassemia major and sickle cell disease were not found. Anemic status or MCV/MCH parameters were not found to be reliable predictors of thalassemia carrier status among the healthy populations of HP. The predominant mutation found was IVS 1–5 G > C.
CONCLUSION:
Popular ongoing strategy for screening with MCV and MCH has low-PPV and can miss upto 37% of true thalassemia carriers. HPLC is better strategy for screening carriers and reduces further spread of thalassemia.
The frequency of Y chromosome microdeletions was studied on idiopathic infertile males with normal karyotype. Genomic DNA was isolated from peripheral blood and PCR analysis was carried out with STS markers -SY 158 and SY 254 to detect the AZFc mutations. Out of 50 infertile males analyzed, four males exhibited AZFc deletions. The SY 158 deletions were observed in three males, viz., azoospermic, severe oligozoospermic and oligozoospermic males. In one azoospermic male SY 254 deletion was observed.
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