{
  "abstract": "Background Sensorineural hearing impairment (SNHI) is a common disorder with a significant genetic basis. Standard next-generation sequencing (NGS) often fails to accurately identify pathogenic variants in the STRC gene due to its complex genomic structure, including large rearrangements and a highly homologous pseudogene. Long-read sequencing (LRS) offers improved resolution for these complex regions. Methods We developed a comprehensive workflow that integrates PacBio-based LRS with marker-mediated refinements and MLPA validations to specifically address pseudogene interference. This methodology was applied to analyze the STRC gene in a cohort of 100 unrelated Taiwanese patients with SNHI of unknown genetic origin after initial NGS screening. Results We identified bi-allelic STRC variants in 11 unrelated patients (11% diagnostic yield), including homozygous deletions, compound heterozygous deletions and conversions, and compound heterozygous single nucleotide variants (SNVs) and copy number variants (CNVs). All unrelated cases resolved with bi-allelic STRC variants were affected with mild or moderate SNHI, occupying 15.1% of total 73 mild-to-moderate SNHI patients in this study. Conclusion Our results highlight the diagnostic utility of this combined strategy, integrating LRS with marker-mediated refinements that validated by MLPA assays, in detecting complex STRC variants and advance the understanding of the genetic etiology of SNHI that remains unresolved by conventional NGS approaches. Graphical Abstract",
  "abstract_shown": true,
  "affiliations": [
    "Department of Otolaryngology, National Taiwan University Hospital",
    "Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University",
    "Institute of Molecular and Genomic Medicine, National Health Research Institute"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Cheng-Yu Tsai"
    },
    {
      "affs": [
        0
      ],
      "name": "Yue-Sheng Lu"
    },
    {
      "affs": [
        1
      ],
      "name": "Yu-Ting Chiang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ming-Yu Lo"
    },
    {
      "affs": [
        0
      ],
      "name": "Pei-Hsuan Lin"
    },
    {
      "affs": [
        2
      ],
      "name": "Shih-Feng Tsai"
    },
    {
      "affs": [
        0
      ],
      "name": "Chuan-Jen Hsu"
    },
    {
      "affs": [
        1
      ],
      "name": "Pei-Lung Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Jacob Shu-Jui Hsu"
    },
    {
      "affs": [
        0
      ],
      "name": "Chen-Chi Wu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c3ssv7r7v2kq0.bib",
  "cited_by": 0,
  "doi": "10.1186/s10020-026-01553-x",
  "fulltext_url": "https://doi.org/10.1186/s10020-026-01553-x",
  "id": "c3ssv7r7v2kq0",
  "issns": [
    "1528-3658",
    "1076-1551"
  ],
  "landing_url": "https://doi.org/10.1186/s10020-026-01553-x",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QD415-436"
    ],
    [
      "lcc",
      "RM1-950"
    ],
    [
      "openalex",
      "2809|Hearing, Cochlea, Tinnitus, Genetics"
    ]
  ],
  "openalex": "W7168087169",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/c3ssv7r7v2kq0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:46:03Z",
      "native_id": "91fd6555ed2c47be879e5e2099cb1076",
      "source": "doaj",
      "url": "https://doi.org/10.1186/s10020-026-01553-x"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2809|Hearing, Cochlea, Tinnitus, Genetics",
      "subfield": "neuroscience"
    }
  ],
  "title": "Integrated analysis of STRC variants in hereditary hearing impairment using maker-mediated refinement of long-read sequencing with MLPA validation",
  "title_text": "Integrated analysis of STRC variants in hereditary hearing impairment using maker-mediated refinement of long-read sequencing with MLPA validation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:03Z",
  "url": "https://research.draconitic.com/paper/c3ssv7r7v2kq0",
  "venue": "Molecular Medicine",
  "versions": []
}