{
  "id": 5491314,
  "title": "Developmental pleiotropy revealed by mosaic heterozygous Snrpb deletion underlies CCMS-like axial skeletal defects",
  "url": "https://urgent.news/2026/09/03/developmental-pleiotropy-revealed-by-mosaic-heterozygous-snrpb",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-03T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.02.748635v1?rss=1"
  },
  "original_language": "en",
  "account": "Cerebro-Costo-Mandibular Syndrome (CCMS), a rare congenital disorder, is caused by pathogenic variants in the gene SNRPB. Individuals with this condition have axial skeletal abnormalities such as cleft palate, micrognathia, posterior rib gaps, and a bell-shaped thorax. The molecular mechanisms behind these axial defects are not well understood, which hinders the development of targeted treatments. Researchers created a mouse model with CCMS-like attributes using an inducible Cre-lox system to conditionally delete Snrpb. When exons 2-3 of Snrpb were deleted after gastrulation, the model displayed all CCMS-like abnormalities, including micrognathia, posterior rib gaps, and a smaller thoracic cavity. However, the somites still formed normally and were properly patterned. Further analysis showed that mutation in Snrpb led to increased expression of p53 pathway genes and abnormal retinoic acid (RA) signaling components. Additionally, some alternatively spliced genes in mutant somites were linked to post-transcriptional regulation, including chromatin modifiers. An attempt to alleviate the axial defects by supplementing the diet with RA failed, suggesting that p53 activation and chromatin dysregulation also play significant roles in the disease's development. Overall, this study presents the first in vivo model of CCMS-related axial skeletal abnormalities and demonstrates that Snrpb dysfunction disrupts the initial development of axial skeletal identity without affecting somite patterning.",
  "summary": "Cerebro-Costo-Mandibular Syndrome (CCMS) is a rare congenital disorder due to pathogenic variants in the core spliceosomal gene SNRPB. Affected individuals present with axial skeletal abnormalities, including cleft palate, micrognathia, posterior rib gaps, and a bell-shaped thorax. The molecular basis of these axial defects remains poorly understood, limiting the development of targeted…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}