{
  "abstract": "Dyggve-Melchior-Clausen disease (DMC) is a rare skeletal dysplasia caused by biallelic variants in DYM. We investigated four affected individuals from three families with classical DMC features and non-diagnostic whole-exome sequencing. Reanalysis identified a homozygous deep intronic variant, DYM: c.193+132G>T, in Family 1 and a homozygous 331-bp AluYb8 insertion in exon 12 in Family 2. CRISPR prime editing and transcript analysis demonstrated that c.193+132G>T activates cryptic splice sites, resulting in 13-bp and 67-bp pseudoexon inclusion predicted to disrupt the reading frame. A missense variant of uncertain significance was identified in Family 3. These findings expand the mutational spectrum of DYM and highlight the value of investigating non-coding and structural variants in patients with a strong DMC phenotype.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "Prince Jacob",
      "orcid": "0000-0002-3343-3262"
    },
    {
      "name": "Lingjuan Hong",
      "orcid": "0000-0001-6069-7725"
    },
    {
      "name": "Deepa Bhat",
      "orcid": "0000-0002-4928-1718"
    },
    {
      "name": "KN Gopika",
      "orcid": "0009-0008-0297-8893"
    },
    {
      "name": "Shushu Huang",
      "orcid": "0000-0002-0220-4395"
    },
    {
      "name": "Benjamin Kramer",
      "orcid": "0009-0006-4140-6017"
    },
    {
      "name": "K Mohandas Nair"
    },
    {
      "name": "Monkol Lek",
      "orcid": "0000-0003-1227-6293"
    },
    {
      "name": "Siddaramappa J Patil",
      "orcid": "0000-0001-7154-3449"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f5vsq3t6g2q9f.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.22.26365648",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.10.22.26365648v1.full",
  "id": "f5vsq3t6g2q9f",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.10.22.26365648v1",
  "language": "en",
  "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",
      "Article"
    ],
    [
      "medrxiv",
      "genetic and genomic medicine"
    ],
    [
      "openalex",
      "1311|Genomics and Rare Diseases"
    ]
  ],
  "openalex": "W7223673893",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.10.22.26365648v1.full.pdf",
  "pmcid": "PMC13734049",
  "pmid": "42990333",
  "published": "2026-10-22",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/f5vsq3t6g2q9f.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:51Z",
      "native_id": "10.64898/2026.10.22.26365648",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.10.22.26365648v1"
    },
    {
      "first_seen": "2026-11-08T12:23:42Z",
      "native_id": "PMC13734049",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.22.26365648"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:genetic and genomic medicine",
      "subfield": "human-genetics"
    }
  ],
  "title": "Rare Genetic Mechanisms in Dyggve-Melchior-Clausen Disease",
  "title_text": "Rare Genetic Mechanisms in Dyggve-Melchior-Clausen Disease",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:42Z",
  "url": "https://research.draconitic.com/paper/f5vsq3t6g2q9f",
  "venue": "medRxiv",
  "versions": []
}