{
  "abstract": "Background: The melanocortin-1 receptor (MC1R) gene is a major determinant of skin and hair color. Although several MC1R variants increase the risk of skin tumors regardless of pigmentation, their role as genetic modifiers in ocular diseases remains poorly understood. Methods: Here, we analyzed a cohort of 48 Caucasian individuals using a custom next-generation sequencing (NGS) panel targeted for oculocutaneous disorders. Results:MC1R variants were identified in two probands selected from this cohort, exhibiting distinctly divergent pathological phenotypes. The first patient, an adult male with a pheomelanin-related trait and a history of early-onset skin cancer without ocular abnormalities, carried compound heterozygous MC1R variants: the novel frameshift c.537dupC (p.Ile180Hisfs*59) and the known c.880G>C (p.Asp294His). Conversely, the second patient, a young boy with severe vision-threatening features-including congenital nystagmus, foveal hypoplasia, and an atypical visual-pathway misrouting pattern-carried a candidate digenic genotype combining the same MC1R c.880G>C variant with the albinism-related c.1209G>T (p.Arg403Ser) variant in the tyrosinase (TYR) gene. Conclusions: While MC1R variants have previously been proposed as phenotypic modifiers in albinism, primarily in combination with the oculocutaneous type II melanosomal transmembrane protein (OCA2) encoding gene, our findings support a potential role for MC1R as a candidate modifier interacting with TYR in neuroretinal development. Although functional validation is required to establish causality, incorporating MC1R screening in patients with unresolved foveal hypoplasia may help clarify complex oligogenic mechanisms and optimize phenotypic classification.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Molecular Medicine, University of Padova, 35121 Padova, Italy.",
    "Clinical Genetics Unit, Department of Integrated Diagnostic Services, University Hospital of Padova, 35128 Padova, Italy.",
    "Center for Retinitis Pigmentosa of Veneto Region (ERN-EYE Network), Camposampiero Hospital, Azienda ULSS 6 Euganea, 35121 Padova, Italy.",
    "Department of Translational Medicine and for Romagna, University of Ferrara, 44121 Ferrara, Italy.",
    "Medical Genetics Unit, Treviso Hospital, 31100 Treviso, Italy.",
    "Department of Women's and Children's Health, University of Padova, 35121 Padova, Italy.",
    "Fondazione Banca degli Occhi del Veneto ETS, 30174 Venice, Italy.",
    "King Khaled Eye Specialist Hospital, Riyadh 12211, Saudi Arabia.",
    "Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy.",
    "Robert Hollman Foundation, 35121 Padova, Italy.",
    "Fondazione Banca dei Tessuti del Veneto ETS, 31100 Treviso, Italy."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Enzo Di Iorio",
      "orcid": "0000-0001-7616-4958"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Francesco Parmeggiani",
      "orcid": "0000-0002-9296-0986"
    },
    {
      "affs": [
        4
      ],
      "name": "Antonella De Nardi"
    },
    {
      "affs": [
        5
      ],
      "name": "Francesco Prevedello",
      "orcid": "0009-0004-8950-8595"
    },
    {
      "affs": [
        5
      ],
      "name": "Rebecca Affuso"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Anna Demarinis",
      "orcid": "0009-0001-8172-9797"
    },
    {
      "affs": [
        1
      ],
      "name": "Andrea Gazzin",
      "orcid": "0000-0002-5230-2831"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Chiara Rigon"
    },
    {
      "affs": [
        6
      ],
      "name": "Vanessa Barbaro",
      "orcid": "0000-0001-8760-2343"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Katia De Nadai"
    },
    {
      "affs": [
        3
      ],
      "name": "Antonio Cartabellotta",
      "orcid": "0009-0000-5855-459X"
    },
    {
      "affs": [
        3
      ],
      "name": "Ginevra Giovanna Adamo",
      "orcid": "0009-0001-9417-1200"
    },
    {
      "affs": [
        3,
        7
      ],
      "name": "Marco Mura",
      "orcid": "0000-0001-5283-5366"
    },
    {
      "affs": [
        2,
        8,
        9
      ],
      "name": "Agnese Suppiej",
      "orcid": "0000-0001-5130-1450"
    },
    {
      "affs": [
        0,
        10
      ],
      "name": "Giorgio Palù"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Leonardo Salviati",
      "orcid": "0000-0001-5642-9963"
    },
    {
      "affs": [
        2
      ],
      "name": "Marco Tavolato"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a02w8fxyrksha.bib",
  "cited_by": 0,
  "doi": "10.3390/genes17101289",
  "fulltext_url": "https://europepmc.org/articles/PMC13703980",
  "id": "a02w8fxyrksha",
  "issns": [
    "2073-4425"
  ],
  "landing_url": "https://europepmc.org/article/MED/42938405",
  "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",
      "1307|melanin and skin pigmentation"
    ]
  ],
  "openalex": "W7221955626",
  "pdf_url": "https://europepmc.org/articles/PMC13703980?pdf=render",
  "pmcid": "PMC13703980",
  "pmid": "42938405",
  "published": "2026-10-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/a02w8fxyrksha.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:12Z",
      "native_id": "MED:42938405",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42938405"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|melanin and skin pigmentation",
      "subfield": "cell-biology"
    }
  ],
  "title": "Evaluating the Role of MC1R Variants in Cutaneous and Ocular Phenotypes: A Candidate TYR-MC1R Genetic Interaction in Oculocutaneous Disorders.",
  "title_text": "Evaluating the Role of MC1R Variants in Cutaneous and Ocular Phenotypes: A Candidate TYR-MC1R Genetic Interaction in Oculocutaneous Disorders.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:12Z",
  "url": "https://research.draconitic.com/paper/a02w8fxyrksha",
  "venue": "Genes",
  "versions": []
}