Focused Exome Sequencing Gives a High Diagnostic Yield in the Indian Subcontinent.

The genetically isolated yet heterogeneous and highly consanguineous Indian population has shown a higher prevalence of rare genetic disorders. However, there is a significant socioeconomic burden for genetic testing to be accessible to the general population. In the current study, we analyzed next-generation sequencing data generated through focused exome sequencing from individuals with different phenotypic manifestations referred for genetic testing to achieve a molecular diagnosis. Pathogenic or likely pathogenic variants are reported in 280 of 833 cases with a diagnostic yield of 33.6%. Homozygous sequence and copy number variants were found as positive diagnostic findings in 131 cases (15.7%) because of the high consanguinity in the Indian population. No relevant findings related to reported phenotype were identified in 6.2% of the cases. Patients referred for testing due to metabolic disorder and neuromuscular disorder had higher diagnostic yields. Carrier testing of asymptomatic individuals with a family history of the disease, through focused exome sequencing, achieved positive diagnosis in 54 of 118 cases tested. Copy number variants were also found in trans with single-nucleotide variants and mitochondrial variants in a few of the cases. The diagnostic yield and the findings from this study signify that a focused exome test is a good lower-cost alternative for whole-exome and whole-genome sequencing and as a first-tier approach to genetic testing.

Randomized, double-blind, comparative study of oral metronidazole and tinidazole in treatment of bacterial vaginosis.

OBJECTIVE: To compare the efficacy and tolerability of oral metronidazole and tinidazole in patients with bacterial vaginosis (BV) using Amsel's criteria. PATIENTS AND METHODS: This was a randomized double-blind study, conducted by the Departments of Pharmacology and Gynecology of a tertiary care teaching hospital. Patients diagnosed with BV received either tablet metronidazole 500 mg twice daily for 5 days or tablet tinidazole 500 mg once daily + one placebo for 5 days and instructed to come for follow-up at the 1st week and 4th week. They were categorized as cured, partially cured, and not cured based on Amsel's criteria at the end of the study and compared between two groups using Chi-square test. RESULTS: A total 120 women were enrolled in the study, of which 114 completed the study. The treatment arms were comparable. The cure rate with low-dose tinidazole was significantly more compared to metronidazole at 4th week (P = 0.0013), but not at 1st week (P = 0.242). The adverse drug reactions were less with tinidazole compared to metronidazole. CONCLUSION: Tinidazole at lower dose offers a better efficacy than metronidazole in long-term cure rates and in preventing relapses with better side effect profile.