Background and Objectives: Hereditary hearing loss is the most common genetic disorder in children. Nearly 120 genes associated with auditory impairment have been identified. Although the disease is clinically and genetically complex, the chances of identifying deafness-causing loci increase when studying consanguineous families.Materials and Methods: Whole-exome sequencing was performed to identify genetic variants underlying sensorineural hearing loss in affected individuals from a family with third-degree consanguineous practices.Results: A homozygous deletion of 250.285 kb was identified in the 16p12.2 region encompassing three genes, METTL9, IGSF6, and OTOA, and a partial deletion of the NPIPB4 gene co-segregated within the family.Conclusions: This study highlighted the genetic heterogeneity of hearing loss in consanguineous families. Future research should focus on the OTOA mutational spectrum in South Indian populations with hearing loss.

Background: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects women of reproductive age, often associated with metabolic issues, causing infertility. Although it is common, the cause of PCOS remains unknown, and early diagnosis is challenging. MicroRNAs (miRNAs) serve as post-transcriptional regulators of gene expression, play a significant role in PCOS development, and have emerged as biomarkers for reproductive and metabolic disorders. However, research on miRNA signatures in the Indian population is limited. This pilot exploratory study aims to compare the candidate differentially expressed miRNAs (DE miRNAs) in serum samples from individuals with and without PCOS using high-throughput miRNA sequencing. Methods: In the study, patients with PCOS and age-matched controls were included; small RNAs were isolated from their serum, libraries were prepared, and the libraries were analyzed by next-generation sequencing. Bioinformatics analysis, including miRBase annotation, differential expression analysis, target prediction, GO/KEGG enrichment, and hub gene network analysis, was performed. Results: A total of 967 miRNAs were identified, with seven showing differential expression (log2FC > 1, p < 0.05). Among these, six miRNAs of hsa-miR-219a-2-3p, hsa-mir-384, hsa-miR-149-5p, hsa-miR-3182, hsa-miR-3960, and hsa-miR-4508 were upregulated, whereas hsa-mir-139 was downregulated. Functional enrichment and hub gene analyses identified key targets, including TP53, FOXO1, HIF1A, and HDAC1, that are crucial to the cell cycle, insulin signaling, and hypoxia. Conclusions: These preliminary findings identify candidate serum miRNA signatures in Indian women that may be associated with PCOS’s reproductive and metabolic issues. These pilot study results suggest potential miRNAs and their target pathway links with PCOS that need validation in larger cohorts for diagnostic or therapeutic applications.

Background and Objectives: Hereditary hearing loss is the most common auditory disability among various disabilities. Consanguineous populations have been found to have autosomal recessive disorders twice as often as in the general population. This study aimed to highlight the phenotypic and genetic complexity of non-syndromic hearing loss (NSHL) in South Indian consanguineous families. Materials and Methods: Whole-exome sequencing (WES) was performed on individuals with NSHL who were negative for common deafness-causing genes (GJB2, GJB6, SLC26A4, and MTRNR1). The candidate variants identified were correlated with ROH regions identified using the Automap tool. Sanger sequencing was performed for validation, followed by segregation analysis for the available family members. The effects of the candidate variants were analyzed using an in silico structural approach and the ACMG guidelines. Results: WES identified variants, including a stop-gain, an indel, and a missense mutation, in the genes SIX1, MYO7A, MYO3A, and MYO15A. Three variants were classified as likely pathogenic, one variant as a variant of uncertain significance (VUS), and one variant as likely benign. Homozygous variants in MYO15A and MYO7A were identified within ROH regions, indicating autosomal recessive inheritance. Additionally, two heterozygous variants in the SIX1 and MYO3A genes were identified. This study indicates a high degree of genotypic and phenotypic heterogeneity of hearing loss among affected individuals. Conclusions: This integrated approach, which combines homozygosity mapping with WES, could be effective for diagnosing NSHL in affected individuals. Further genetic screening and characterization of NSHL in consanguineous families is also warranted. Genetic testing in high-risk populations could be a valuable method for diagnosing genetic hearing loss in children.