{
  "abstract": "ObjectiveWe analyzed 190 PROM1 variants to determine whether we could identify genotype-phenotype correlations with predictive value for patient outcomes. We present a case-series of 7 patients with rare, under-reported, or unique forms of PROM1-associated retinal dystrophies.\n\nDesignWe performed a retrospective database study by searching for human PROM1 variants reported to be pathogenic, likely pathogenic, or disease-causing in two online databases: ClinVar and Human Gene Mutation Database. Contingency tables were constructed variable pairs - inheritance pattern vs. variant type, inheritance pattern vs. reported phenotype, inheritance pattern vs. protein domain, phenotype vs. variant type, phenotype vs. protein domain, and variant type vs. protein domain - and were then analyzed using a Monte Carlo chi-square test of independence with adjusted standardized residuals. Cells with absolute standardized residuals [≤] -1.96 and [≥] 1.96 were interpreted as under- or over-represented relative to expectation (p < 0.05).\n\nParticipantsSeven participants with PROM1-associated retinal degeneration were contacted from our ocular genetics clinical practice; all contacted patients or legal guardians consented to be included in this case-series.\n\nMain Outcome(s) and Measure(s)The primary study outcome was to determine whether there were any meaningful genotype-phenotype relationships for disease-causing PROM1 variants by chi-square correlation analysis. Patient case-series were included to enrich statistical findings.\n\nResultsWe found a meaningful increase in observed counts of autosomal dominant missense variants associated with macular dystrophy. Of 7 patients, 3 were women (43%) and ages ranged from 4-58 years. Four of the seven patients had dominantly inherited missense variants (c.1117C>T, c.1557C>A, c.2110C>T, c.1655T>C). Recessive patient variants were all predicted to generate a truncated protein, including two patients with the same variant (c.1423_1424del), and a patient with a c.1354dup variant and compound heterozygous ABCA4 variants of unknown significance (c.2382+95A, c.-79C>T). All patient phenotypes were in agreement with predicted phenotypic outcomes from our statistical analysis.\n\nConclusionsWe provided statistical outcomes and patient case-series data that support predictive value for dominant and recessive forms of PROM1-associated inherited retinal degeneration. These data could inform expected outcomes for patients with PROM1-associated blindness, lessoning anxiety about unknown outcomes, and provide a framework to inform best-practices for patient follow-up.",
  "abstract_shown": true,
  "affiliations": [
    "University of Alberta"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "M. Shoukat"
    },
    {
      "name": "K. M. Papp"
    },
    {
      "name": "E. Misaghi"
    },
    {
      "name": "D. J. Kalra"
    },
    {
      "name": "I. M. MacDonald"
    },
    {
      "name": "M. D. Benson"
    },
    {
      "affs": [
        0
      ],
      "name": "B. J. Carr"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e84j6g7sct8sh.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.03.26361572",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.03.26361572v1.full",
  "id": "e84j6g7sct8sh",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.03.26361572v1",
  "language": null,
  "licence": "CC-BY-ND",
  "licence_label": "CC BY-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "ophthalmology"
    ],
    [
      "openalex",
      "1312|Retinal Development and Disorders"
    ]
  ],
  "openalex": "W7211906458",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.03.26361572v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e84j6g7sct8sh.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:51Z",
      "native_id": "10.64898/2026.09.03.26361572",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.03.26361572v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Retinal Development and Disorders",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Genotype-Phenotype Correlations Reveal Positive Inheritance and Phenotype Associations for PROM1-Associated Inherited Retinal Degenerations",
  "title_text": "Genotype-Phenotype Correlations Reveal Positive Inheritance and Phenotype Associations for PROM1-Associated Inherited Retinal Degenerations",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:51Z",
  "url": "https://research.draconitic.com/paper/e84j6g7sct8sh",
  "venue": "medRxiv",
  "versions": []
}