{
  "abstract": "IntroductionRing chromosome 21 (r (21)) is a rare constitutional rearrangement involving terminal deletions and significant phenotypic heterogeneity. High-resolution genomic analyses have demonstrated that ring chromosomes may harbor complex genomic imbalances and dynamic mosaicism. However, the contributions of ring chromosome instability, tissue-specific mosaicism, and complex dosage imbalance to the clinical phenotype remain poorly understood.Case PresentationWe report an 8-month-old boy with developmental delay, congenital heart disease, hearing impairment, structural brain abnormalities, and dysmorphic features suggestive of Down syndrome (DS), although lacking the complete classical phenotype. Cytogenomic analyses identified a constitutional non-supernumerary r (21) associated with a 18.77-Mb duplication of 21q21.2-q22.3 and a 3.09-Mb terminal deletion of 21q22.3. Fluorescence in situ hybridization (FISH) resolved the ring chromosome structure, identifying four instability-derived clones, and demonstrated tissue-specific mosaicism across lymphocytes, oral mucosa epithelial cells, and urinary sediment epithelial cells, with a duplicated monocentric r (21) as the predominant clone. Comparison with the four previously reported constitutional non-supernumerary r (21) cases revealed a recurrent combination of Down syndrome critical region (DSCR) duplication and terminal 21q deletion, despite substantial phenotypic variability.Discussion and ConclusionThis study expands the clinical and cytogenomic spectrum associated with constitutional non-supernumerary r (21). Tissue-specific mosaicism and recurrent genomic imbalances suggest that the DS-like phenotype cannot be explained solely by dosage alterations involving the classical or highly restricted DSCR. Our findings suggest a mechanism in which dynamic ring chromosome instability, and the cumulative dosage imbalance of multiple chromos​ome 21 genes, contribute to the phenotypic variability observed in these patients. Additional well-characterized cases are essential for refining the genotype–phenotype correlations of this rare genomic disorder.",
  "abstract_shown": true,
  "affiliations": [
    "Genetics and Cancer Laboratory, National Pediatric Institute, Mexico City, Mexico",
    "Department of Human Genetics, National Pediatric Institute, Mexico City, Mexico",
    "Specialized Genetic Analysis Laboratory Mexico (LAGEM), Mexico City, Mexico"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Daniel Martínez Anaya"
    },
    {
      "affs": [
        0
      ],
      "name": "Alejandro Zinser Sainas"
    },
    {
      "affs": [
        1
      ],
      "name": "Marelen Cruz Cruz"
    },
    {
      "affs": [
        1
      ],
      "name": "Ana Lucía Yáñez-Félix"
    },
    {
      "affs": [
        0
      ],
      "name": "Consuelo Salas Labadía"
    },
    {
      "affs": [
        0
      ],
      "name": "Carlos Andre Orta Barcenas"
    },
    {
      "affs": [
        2
      ],
      "name": "David Arturo Sosa Sánchez"
    },
    {
      "affs": [
        1
      ],
      "name": "Emiy Yokoyama Rebollar"
    },
    {
      "affs": [
        0
      ],
      "name": "Patricia Pérez-Vera"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4kj24xjg21z86.bib",
  "cited_by": 0,
  "doi": "10.3389/fgene.2026.1958717",
  "fulltext_url": "https://www.frontiersin.org/articles/10.3389/fgene.2026.1958717/full",
  "id": "4kj24xjg21z86",
  "issns": [
    "1664-8021"
  ],
  "landing_url": "https://doi.org/10.3389/fgene.2026.1958717",
  "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"
    ],
    [
      "openalex",
      "1311|Genomic variations and chromosomal abnormalities"
    ]
  ],
  "openalex": "W7223562683",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-25",
  "publisher": "Frontiers Media S.A.",
  "ris": "https://research.draconitic.com/paper/4kj24xjg21z86.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:46:52Z",
      "native_id": "1611ab17a07f413faa21323b15c50eb8",
      "source": "doaj",
      "url": "https://doi.org/10.3389/fgene.2026.1958717"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Genomic variations and chromosomal abnormalities",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Dynamic tissue-specific mosaicism in constitutional non-supernumerary ring chromosome 21 with a Down syndrome-like phenotype: a case report and genotype-phenotype analysis",
  "title_text": "Dynamic tissue-specific mosaicism in constitutional non-supernumerary ring chromosome 21 with a Down syndrome-like phenotype: a case report and genotype-phenotype analysis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T14:20:56Z",
  "url": "https://research.draconitic.com/paper/4kj24xjg21z86",
  "venue": "Frontiers in Genetics",
  "versions": []
}