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<p>Non-syndromic hearing loss (NSHL) is a genetically heterogeneous disorder affecting millions worldwide. Recent advances in genetic technologies have expanded our understanding of its molecular basis, but challenges remain in identifying and interpreting causative variants. This study aimed to investigate the genetic etiology of NSHL using comprehensive genetic screening, with a focus on identifying rare and potentially pathogenic variants. We performed genetic analysis on 43 participants diagnosed with NSHL using whole exome sequencing (WES) technology. Variant filtering, <i>in silico</i> prediction tools, and segregation analysis were employed to evaluate the pathogenicity of identified variants. Our analysis revealed 20 rare and deleterious variants (4 novel and 16 previously reported) in 16 NSHL-related genes among 43 participants. These variants included 3 known pathogenic, 4 likely pathogenic, and 13 variants of uncertain significance (VUS). Notably, we identified compound heterozygous variants in the <i>GPSM2</i> gene (NM_013296:c.185G&gt;A;p.Ser62Asn and NM_013296:c.1264delG;p.Val422Tyrfs*28) in one participant, with segregation analysis confirming their <i>trans</i> configuration. This study expands our understanding of the genetic landscape of NSHL by identifying several rare variants in known NSHL-related genes. Notably, we report the first case of compound heterozygous variants in the <i>GPSM2</i> gene in the Indian population, a finding not previously documented. This discovery underscores the importance of comprehensive genetic screening in diverse populations and contributes to the growing body of evidence for the role of <i>GPSM2</i> in NSHL.</p>

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Whole exome sequencing reveals novel and rare variants in non-syndromic hearing loss-related genes: A focus on GPSM2 compound heterozygosity

  • 期刊论文

  • 发表日期：

    2025年5月5日

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  • Sudipta Chakraborty,
  • Sukanya Mitra,
  • Arnab Ghosh,
  • Krishna Kumar,
  • Shamita Sanga,
  • Atanu Kumar Dutta,
  • Suchandra Mukherjee,
  • Nidhan Kumar Biswas,
  • Saikat Chakrabarti,
  • Moulinath Acharya

摘要

Non-syndromic hearing loss (NSHL) is a genetically heterogeneous disorder affecting millions worldwide. Recent advances in genetic technologies have expanded our understanding of its molecular basis, but challenges remain in identifying and interpreting causative variants. This study aimed to investigate the genetic etiology of NSHL using comprehensive genetic screening, with a focus on identifying rare and potentially pathogenic variants. We performed genetic analysis on 43 participants diagnosed with NSHL using whole exome sequencing (WES) technology. Variant filtering, in silico prediction tools, and segregation analysis were employed to evaluate the pathogenicity of identified variants. Our analysis revealed 20 rare and deleterious variants (4 novel and 16 previously reported) in 16 NSHL-related genes among 43 participants. These variants included 3 known pathogenic, 4 likely pathogenic, and 13 variants of uncertain significance (VUS). Notably, we identified compound heterozygous variants in the GPSM2 gene (NM_013296:c.185G>A;p.Ser62Asn and NM_013296:c.1264delG;p.Val422Tyrfs*28) in one participant, with segregation analysis confirming their trans configuration. This study expands our understanding of the genetic landscape of NSHL by identifying several rare variants in known NSHL-related genes. Notably, we report the first case of compound heterozygous variants in the GPSM2 gene in the Indian population, a finding not previously documented. This discovery underscores the importance of comprehensive genetic screening in diverse populations and contributes to the growing body of evidence for the role of GPSM2 in NSHL.