{
  "abstract": "Normal human linear growth depends on intact growth hormone (GH) signaling and insulin-like growth factor-I (IGF-I) bioavailability. In the circulation, IGF-I is largely bound to IGF-binding proteins (IGFBPs), predominantly IGFBP-3 and IGFBP-5, which, together with the acid-labile subunit form a ternary complexes that prolong its half-life. Pregnancy-associated plasma protein-A2 (PAPP-A2) cleaves IGFBP-3 and IGFBP-5, releasing bioactive IGF-I. Pathogenic PAPPA2 variants impair this process, reducing IGF-I bioavailability despite elevated total IGF-I concentrations. We report a 12.3-year-old Jordanian girl with short stature and delayed dental development. Biochemical evaluation demonstrated markedly elevated serum IGF-I and high-normal IGFBP-3. Comparative genomic hybridization microarray and targeted sequencing of genes associated with postnatal growth failure, including IGF1R, were unremarkable. A 6-month trial of recombinant human GH produced no measurable growth acceleration; however, interpretation was limited because treatment was commenced when skeletal maturity was advanced. Extended genetic analysis subsequently identified a novel homozygous PAPPA2 frameshift variant, c.1223delT (p.L408Rfs*49). This case expands the molecular spectrum of PAPP-A2 deficiency and highlights the importance of PAPPA2 testing in children with short stature, persistently elevated total IGF-I, and negative IGF1R genetic analysis. Delayed dental development may provide an additional clinical clue and help distinguish PAPP-A2 deficiency from other causes of short stature.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pediatric Endocrinology, Etlik City Hospital, University of Health Sciences, Ankara 06170, Turkey.",
    "Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University, London EC1M 6BQ, UK.",
    "Department of Paediatric Endocrinology, Bristol Royal Hospital for Children, Bristol BS2 8BJ, UK.",
    "Bristol Medical School, University of Bristol, Queens Road, Bristol BS8 1QU, UK."
  ],
  "article_type": "case report",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Erdal Kurnaz",
      "orcid": "0000-0002-1814-3216"
    },
    {
      "affs": [
        1
      ],
      "name": "Avinaash Vickram Maharaj",
      "orcid": "0000-0001-8051-3866"
    },
    {
      "affs": [
        1
      ],
      "name": "Afiya Andrews",
      "orcid": "0000-0003-2390-657X"
    },
    {
      "affs": [
        1
      ],
      "name": "Helen L Storr"
    },
    {
      "affs": [
        2
      ],
      "name": "Sumana Chatterjee"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Dinesh Giri",
      "orcid": "0000-0001-8129-1978"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/817srw6qx7m4a.bib",
  "cited_by": 0,
  "doi": "10.1210/jcemcr/luag317",
  "fulltext_url": "https://europepmc.org/articles/PMC13712125",
  "id": "817srw6qx7m4a",
  "issns": [
    "2755-1520"
  ],
  "landing_url": "https://europepmc.org/article/MED/42948660",
  "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",
      "AcademicSubjects/MED00010"
    ],
    [
      "heading",
      "AcademicSubjects/MED00160"
    ],
    [
      "heading",
      "AcademicSubjects/MED00250"
    ],
    [
      "heading",
      "AcademicSubjects/MED00300"
    ],
    [
      "heading",
      "AcademicSubjects/MED00905"
    ],
    [
      "heading",
      "Case Report"
    ],
    [
      "openalex",
      "2712|Growth Hormone and Insulin-like Growth Factors"
    ]
  ],
  "openalex": "W7223811192",
  "pdf_url": "https://europepmc.org/articles/PMC13712125?pdf=render",
  "pmcid": "PMC13712125",
  "pmid": "42948660",
  "published": "2026-10-27",
  "publisher": "Oxford University Press",
  "ris": "https://research.draconitic.com/paper/817srw6qx7m4a.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:33Z",
      "native_id": "MED:42948660",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42948660"
    },
    {
      "first_seen": "2026-10-31T12:22:46Z",
      "native_id": "PMC13712125",
      "source": "pmc",
      "url": "https://doi.org/10.1210/jcemcr/luag317"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2712|Growth Hormone and Insulin-like Growth Factors",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "Delayed dental development and short stature associated with a novel homozygous PAPPA2 variant.",
  "title_text": "Delayed dental development and short stature associated with a novel homozygous PAPPA2 variant.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:46Z",
  "url": "https://research.draconitic.com/paper/817srw6qx7m4a",
  "venue": "JCEM case reports",
  "versions": []
}