{
  "abstract": "POLR3A-related leukodystrophy is a multisystem disorder classically defined by hypomyelination, hypodontia, and hypogonadotropic hypogonadism (4H syndrome). While neurological and endocrine features are well-defined, the ocular phenotypic spectrum remains incomplete. We present a 15.9-year-old female with a classic 4H phenotype and compound heterozygosity for 2 novel variants (NM_007055.4:c.2102G > T [p.(Gly701Val)] and NM_007055.4:c.2989C > T [p.(Pro997Ser)]). The patient exhibited advanced, rapidly progressive bilateral keratoconus, with a maximum keratometry (K-max) reaching an extreme 75.9 diopter (D). K-max of 75.9 D (approximately 40-47 D in children and adolescents) represents extreme corneal ectasia. Longitudinal follow-up documented progressive ectasia, treated with penetrating keratoplasty in the left eye and corneal collagen cross-linking in the right eye. On the postoperative Pentacam examination at age 22, right-eye K-max was 70.7 D (66.7 D at age 10), and the thinnest location was 304 µm; left-eye values were unreliable owing to automated quality alerts. This case highlights progressive keratoconus as a potential clinical component of POLR3A-related disorders. We propose that ribonucleic acid polymerase III is essential for corneal proteostasis. Our findings position keratoconus as a potential early clinical sentinel for 4H syndrome, necessitating mandatory corneal topography in suspected cases to ensure timely, vision-saving intervention.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Pediatric Endocrinology, Department of Pediatrics, Eskişehir Osmangazi University School of Medicine, Eskişehir 26040, Türkiye.",
    "Department of Ophthalmology, Eskişehir Osmangazi University School of Medicine, Eskişehir 26040, Türkiye.",
    "Department of Medical Genetics, Eskişehir Osmangazi University School of Medicine, Eskişehir 26040, Türkiye."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Enver Simsek",
      "orcid": "0000-0003-0120-9976"
    },
    {
      "affs": [
        1
      ],
      "name": "Tulay Simsek",
      "orcid": "0000-0001-5132-9066"
    },
    {
      "affs": [
        2
      ],
      "name": "Oguz Cilingir",
      "orcid": "0000-0002-5593-4164"
    },
    {
      "affs": [
        1
      ],
      "name": "Eray Atalay",
      "orcid": "0000-0002-2536-4279"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/77ja0vmxbe1bk.bib",
  "cited_by": 0,
  "doi": "10.1210/jcemcr/luag333",
  "fulltext_url": "https://europepmc.org/articles/PMC13740504",
  "id": "77ja0vmxbe1bk",
  "issns": [
    "2755-1520"
  ],
  "landing_url": "https://europepmc.org/article/MED/42996498",
  "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": [
    [
      "openalex",
      "2731|Corneal surgery and disorders"
    ]
  ],
  "openalex": "W7225397492",
  "pdf_url": "https://europepmc.org/articles/PMC13740504?pdf=render",
  "pmcid": "PMC13740504",
  "pmid": "42996498",
  "published": "2026-11-06",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/77ja0vmxbe1bk.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T15:20:34Z",
      "native_id": "MED:42996498",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42996498"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "journal-openalex:2712|Pituitary Gland Disorders and Treatments",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "Novel compound heterozygous POLR3A variation: expanding 4H syndrome with progressive keratoconus.",
  "title_text": "Novel compound heterozygous POLR3A variation: expanding 4H syndrome with progressive keratoconus.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T15:20:34Z",
  "url": "https://research.draconitic.com/paper/77ja0vmxbe1bk",
  "venue": "JCEM case reports",
  "versions": []
}