{
  "abstract": "Background Pseudohypoparathyroidism (PHP) is a heterogeneous disorder caused by genetic or epigenetic changes at the GNAS locus on chromosome 20q13.3 leading to impaired cyclic adenosine monophosphate (cAMP)-dependent signaling pathway via the alpha-subunit of the stimulatory G protein (Gsα). Unlike PHP type 1 A (PHP1A), which occurs due to GNAS variant and low Gsα activity, the activity of Gsα is normal in PHP type 1 C (PHP1C) despite the same phenotypic characteristics as PHP1A. However, the genetic cause of PHP1C is unknown. Methods The likely causative variant of PHP1C was investigated using next-generation sequencing, and Gsα protein levels and function were assessed in patient-derived cells by immunoblotting, immunocytochemistry and cAMP measurement. Results We identified a de novo genomic deletion in a promoter region and 5’ untranslated region (UTR) of GNAS (5’ deletion of GNAS), in a participant with PHP1C. Furthermore, although the mRNA and protein levels of GNAS were maintained, cAMP production was impaired in PHP1C, implicating a functional abnormality rather than quantitative changes. Conclusions This novel 5’-UTR deletion of GNAS may underlie PHP1C and highlights the importance of assessing non-coding regions of GNAS in participants with PHP1C or PHP1A who lack pathogenic variants in conventional genetic tests.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pathology, Yonsei University College of Medicine",
    "Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine",
    "Department of Biochemistry, College of Medicine, Ewha Womans University",
    "Department of Biomedical Science, CHA Stem Cell Institute, CHA University",
    "GC Genome",
    "Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Chung Lee"
    },
    {
      "affs": [
        1
      ],
      "name": "Yoon Ji Ahn"
    },
    {
      "affs": [
        2
      ],
      "name": "Sung-Chul Jung"
    },
    {
      "affs": [
        2
      ],
      "name": "Saeyoung Park"
    },
    {
      "affs": [
        3
      ],
      "name": "Ji Yeon Kim"
    },
    {
      "affs": [
        4
      ],
      "name": "Chang-Seok Ki"
    },
    {
      "affs": [
        5
      ],
      "name": "Woong-Yang Park"
    },
    {
      "affs": [
        1
      ],
      "name": "Sung Yoon Cho"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/58v8td822ejq2.bib",
  "cited_by": 0,
  "doi": "10.1186/s12920-026-02439-x",
  "fulltext_url": "https://doi.org/10.1186/s12920-026-02439-x",
  "id": "58v8td822ejq2",
  "issns": [
    "1755-8794"
  ],
  "landing_url": "https://doi.org/10.1186/s12920-026-02439-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",
      "QH426-470"
    ],
    [
      "lcc",
      "RC31-1245"
    ],
    [
      "openalex",
      "1311|Genetic Syndromes and Imprinting"
    ]
  ],
  "openalex": "W7171562648",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/58v8td822ejq2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:46:30Z",
      "native_id": "07781adc291148cbaec127f11170a477",
      "source": "doaj",
      "url": "https://doi.org/10.1186/s12920-026-02439-x"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Genetic Syndromes and Imprinting",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Genetic evidence linking the promoter region and 5’-UTR deletion of GNAS with pseudohypoparathyroidism type 1 C",
  "title_text": "Genetic evidence linking the promoter region and 5’-UTR deletion of GNAS with pseudohypoparathyroidism type 1 C",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T14:20:51Z",
  "url": "https://research.draconitic.com/paper/58v8td822ejq2",
  "venue": "BMC Medical Genomics",
  "versions": []
}