Mutation Spectrum of ß-Thalassemia in Some Ethnic Groups of North Maharashtra, India.

Beta-thalassemia is the most common inherited single-gene disorder in the world, caused by more than 200 known mutations in the HBB gene. In India, the average prevalence of ß-thalassemia carriers is 3-4%. Several ethnic groups have a much higher prevalence, about 8% in the tribal groups, according to the 2011 census. The study's main goal is to identify common ß-thalassemia mutations and the frequencies of different haplotypes in various communities in North Maharashtra. Nashik district had the highest prevalence of ß-thalassemia (34%), followed by Ahmednagar (29%), Jalgaon (16%), Dhule (14%), and Nandurbar (7.0%). Prevalence of ß-thalassemia was highest in the schedule caste community (SC) (48%), followed by (17%) in Muslims, (14%) in other backward classes (OBC), (13%) in Schedule Tribe (ST), and (8.0%) in the general population The six most common ß-thalassemia mutations detected in this study are IVS 1 > 5 (G→C), Cd 15(G→A), Cd 41/41 (-TCTT), Cd 8/9(+G), IVS 1 > 1(G→T) and Cap + 1(A > G). Among these mutations, IVS 1 > 5 (G > C) was the most common type of mutation found in ß-thalassemia patients in the North Maharashtra population. Type-I haplotype was the most prevalent among all communities. Nashik and Ahmednagar districts were highly affected by ß-thalassemia. Among different ethnic groups, the SC and Muslim communities were the worst affected with a higher proportion of ß-thalassemia and increased frequency of mutations.

Sarcomeric gene mutations in phenotypic positive hypertrophic cardiomyopathic patients in Indian population.

HCM is a monogenic cardiac disorder with a high risk of sudden cardiac death, heterogeneous phenotypic expression and genetic profile. HCM is expressed as autosomal dominant in fashion with the prevalence of 1:500 in the general population. The main objective of the current study was to unravel the mutation status in sarcomeric genes in urbanizing Pune population. HCM patients were recruited from Bharti hospital and Poona hospital and research centre, Pune after being screened by 2-D echocardiography. DNA was extracted from whole blood samples and PCR amplification was performed for selected exons from pre-selected genes, amplimers of >300 b.p were restriction digested and the SSCP technique was optimized for maximum result output. HCM patients shows the maximum prevalence of mitral regurgitation (23.3%) while the minimum prevalence was left auricular diameter (10%). Maximum variation spectrum was present in MYBPC3 genes as most of them were "benign" type as per Polyphen-2 tool status. Mutations in the MYH7 gene produce a prominent impact on splicing by the creation of a new SRP40 binding site (Exon Splicing Enhancer) as predicted by Human Splicing Finder 3.1. I736T mutation in the MYH7 gene results in replacement of ß-strand by α-helix upstream from mutation site which may have a profound impact on protein tertiary structure as predicted by Polyphen-2 tool (probably damaging-1.00). Also, two 'novel' mutations and one 'novel' variation were reported in the present study. Thus, the MYBPC3 gene shows maximum mutation load among other sarcomeric genes. Double gene mutations do not represent much severe pathophysiology as compared to single gene mutated and genotypic negative HCM patients.