{
  "abstract": "Background\n\nPathogenic variants in CFAP65 have been reported in male infertility with sperm motility defects. This study investigated a novel homozygous CFAP65 splice-site variant identified in a consanguineous family in which the proband presented with oligozoospermia and complete asthenozoospermia.Methods\n\nWhole-exome sequencing was performed to identify candidate variants, followed by population- and disease-database annotation. Kinship and runs of homozygosity analyses were used to assess familial relatedness and autozygosity. RNA Splicer prediction and a minigene assay in HEK-293T cells were performed to evaluate the splicing effect of the identified variant.Results\n\nSemen analysis showed a sperm concentration of 8.1 × 10⁶/mL, with total and progressive motility of 0%. Whole-exome sequencing identified a novel homozygous canonical splice-site variant in CFAP65 (NM_194302.4:c.645 + 1G > A), which was classified as pathogenic according to ACMG guidelines. ROH analysis showed increased autosomal homozygosity in the proband (FROH = 7.88%), supporting parental consanguinity. The minigene assay demonstrated complete exon 6 skipping, resulting in a 103-bp transcript deletion and a predicted frameshifted truncated protein p.(Pro182ArgfsTer29).Conclusion\n\nThis study expands the CFAP65 mutational spectrum and supports exon 6 skipping-mediated loss of function as the likely pathogenic mechanism. These findings highlight the value of genetic screening and functional splicing assessment in male infertility with sperm motility defects.",
  "abstract_shown": true,
  "affiliations": [
    "Medical School, the First People's Hospital of Yunnan Province, Kunming University of Science and Technology, Kunming, 650500, China.",
    "State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China.",
    "Department of Medical Genetics, the First People's Hospital of Yunnan Province, Kunming, 650032, China.",
    "Yunnan Provincial Key Laboratory for Birth Defects and Genetic Diseases, National Health Commission Key Laboratory of Preconception Health Birth in Western China, the First People's Hospital of Yunnan Province, Kunming, 650032, China.",
    "Department of Reproductive Medicine, NHC Key Laboratory of Healthy Birth and Birth Defect Prevention in Western China, the First People's Hospital of Yunnan Province, Kunming, 650032, China.",
    "State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China. shih@kust.edu.cn.",
    "Medical School, the First People's Hospital of Yunnan Province, Kunming University of Science and Technology, Kunming, 650500, China. kmzhjie@aliyun.com.",
    "Department of Medical Genetics, the First People's Hospital of Yunnan Province, Kunming, 650032, China. kmzhjie@aliyun.com.",
    "Department of Hematology, the First People's Hospital of Yunnan Province, Kunming, 650032, China. kmzhjie@aliyun.com.",
    "Yunnan Provincial Key Laboratory for Birth Defects and Genetic Diseases, National Health Commission Key Laboratory of Preconception Health Birth in Western China, the First People's Hospital of Yunnan Province, Kunming, 650032, China. kmzhjie@aliyun.com."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Congcong Teng"
    },
    {
      "affs": [
        0,
        2,
        3
      ],
      "name": "Xinhua Tang"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "Lin Li"
    },
    {
      "affs": [
        4
      ],
      "name": "Yaxian Ma"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Yuancun Zhao"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Qing Chen"
    },
    {
      "affs": [
        5
      ],
      "name": "Hong Shi"
    },
    {
      "affs": [
        6,
        7,
        8,
        9
      ],
      "name": "Jie Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ezskr0he3vef7.bib",
  "cited_by": 0,
  "doi": "10.1186/s12920-026-02466-8",
  "fulltext_url": "https://europepmc.org/articles/PMC13670435",
  "id": "ezskr0he3vef7",
  "issns": [
    "1755-8794"
  ],
  "landing_url": "https://europepmc.org/article/MED/42875786",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2743|Sperm and Testicular Function"
    ]
  ],
  "openalex": "W7211950553",
  "pdf_url": "https://europepmc.org/articles/PMC13670435?pdf=render",
  "pmcid": "PMC13670435",
  "pmid": "42875786",
  "published": "2026-09-08",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ezskr0he3vef7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:18Z",
      "native_id": "MED:42875786",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42875786"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2743|Sperm and Testicular Function",
      "subfield": "reproductive-child"
    }
  ],
  "title": "Identification and splicing assessment of a novel homozygous CFAP65 splice-site variant associated with oligozoospermia and complete asthenozoospermia.",
  "title_text": "Identification and splicing assessment of a novel homozygous CFAP65 splice-site variant associated with oligozoospermia and complete asthenozoospermia.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:18Z",
  "url": "https://research.draconitic.com/paper/ezskr0he3vef7",
  "venue": "BMC medical genomics",
  "versions": []
}