{
  "abstract": "Background\n\nP2RX2 encodes the ATP-gated P2X2 receptor associated with autosomal dominant non-syndromic hearing loss 41 (DFNA41). DFNA41 is characterized by progressive sensorineural hearing loss and an increased susceptibility to acoustic trauma. However, the specific phenotypic consequences of truncating or splice-altering variants within this gene remain poorly understood.Methods\n\nWe evaluated a Han Chinese family using a targeted hearing-loss gene panel with segregation analysis. Splicing consequences of a complex indel in P2RX2 exon 2 (NM_174873: c.278_288delinsACGTGAAGCCCCC) were assessed using a pcMINI-C minigene assay, followed by RT-qPCR and Western blotting after expression of the reconstructed aberrant isoforms in heterologous cells.Results\n\nThe proband had early-onset severe-to-profound sensorineural hearing loss and carried a heterozygous P2RX2 complex indel inherited from the father, together with a maternally inherited pathogenic GJB2 frameshift. Minigene assays revealed cryptic splice usage that generated two frameshifted isoforms with premature termination codons. Both mutant isoforms showed reduced steady-state mRNA and markedly reduced P2X2 protein output, consistent with decreased overall P2X2 expression.Conclusion\n\nWe functionally establish that this exon-2 complex indel disrupts splicing and markedly reduces P2X2 output. These findings support a mechanism of loss-of-function and haploinsufficiency. The pronounced intrafamilial variability-manifesting as profound early-onset hearing loss in the proband compared to a milder phenotype in the heterozygous father-underscores the variable expressivity and incomplete penetrance characteristic of P2RX2-linked DFNA41. Although oligogenic modulation is a plausible conceptual framework, it requires cautious interpretation and independent future validation.",
  "abstract_shown": true,
  "affiliations": [
    "Medical Genetic Center, Changzhi Maternal and Child Health Care Hospital , , ,",
    "Department of Pediatrics, Changzhi Maternal and Child Health Care Hospital , , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yilun Tao"
    },
    {
      "affs": [
        0
      ],
      "name": "Wenxia Song"
    },
    {
      "affs": [
        1
      ],
      "name": "Lihong Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Tongli Han"
    },
    {
      "affs": [
        0
      ],
      "name": "Dong Han"
    },
    {
      "affs": [
        1
      ],
      "name": "Luna Hao"
    },
    {
      "affs": [
        1
      ],
      "name": "Chen Zhao"
    },
    {
      "affs": [
        1
      ],
      "name": "Jiangyuan Ping"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoze Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c52hxgz53d7wc.bib",
  "cited_by": 0,
  "doi": "10.3389/fgene.2026.1934538",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13727070/?tool=EBI",
  "id": "c52hxgz53d7wc",
  "issns": [
    "1664-8021"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13727070",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2809|Hearing, Cochlea, Tinnitus, Genetics"
    ]
  ],
  "openalex": "W7222986341",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13727070/pdf/?tool=EBI",
  "pmcid": "PMC13727070",
  "pmid": "42974593",
  "published": "2026-10-20",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/c52hxgz53d7wc.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:50Z",
      "native_id": "PMC:PMC13727070",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13727070"
    },
    {
      "first_seen": "2026-11-04T15:20:48Z",
      "native_id": "MED:42974593",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42974593"
    },
    {
      "first_seen": "2026-11-05T12:23:16Z",
      "native_id": "PMC13727070",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fgene.2026.1934538"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2809|Hearing, Cochlea, Tinnitus, Genetics",
      "subfield": "neuroscience"
    }
  ],
  "title": "A P2RX2 exon-2 complex indel disrupts splicing and reduces P2X2 output: implications for DFNA41 and variable expressivity",
  "title_text": "A P2RX2 exon-2 complex indel disrupts splicing and reduces P2X2 output: implications for DFNA41 and variable expressivity",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:22:52Z",
  "url": "https://research.draconitic.com/paper/c52hxgz53d7wc",
  "venue": "Frontiers in genetics",
  "versions": []
}