Publication

Decoding Clinical Diversity from TGFBR1 and TGFBR2 Mutations

September 19, 2025

🧠 Introduction

Mutations in the TGFBR1 and TGFBR2 genes, central to the Transforming Growth Factor-β (TGFβ) signaling pathway, are known to cause several autosomal-dominant disorders. Despite involving the same genes, these conditions present with strikingly different clinical outcomes, raising critical questions about the underlying mechanisms.

🔍 Research Summary

Our new review in Frontiers in Cell and Developmental Biology explores the wide-ranging effects of TGFBR1 and TGFBR2 mutations. These include connective tissue and cardiovascular disorders such as Loeys-Dietz syndrome, Marfan syndrome type 2, and Thoracic Aortic Aneurysms and Dissections (TAAD), as well as more complex conditions like Shprintzen-Goldberg syndrome and vascular Ehlers-Danlos syndrome. Beyond connective tissue, mutations can even lead to Multiple Self-Healing Squamous Epithelioma (MSSE), a rare familial skin cancer.

The review highlights how mutation location, functional severity (hypomorphicity), dominant-negative effects, and gene–environment interactions contribute to this variability. It also emphasizes the role of disrupted receptor oligomerization and signaling crosstalk in disease development.

🌍 Broader Impact

Understanding why the same mutations can lead to such different clinical pictures is vital for advancing precision medicine. By illuminating the complex genotype–phenotype relationships in these disorders, this research points toward more accurate diagnoses and personalized therapeutic strategies. It also underscores the need for deeper investigation into modifier genes and environmental influences that may shape disease outcomes.

📎 Reference 

@article{AbuSailik2025,
  title = {Decoding clinical diversity in monogenic TGFBR1 and TGFBR2 mutations: insights into the interplay of molecular mechanisms and hypomorphicity},
  volume = {13},
  ISSN = {2296-634X},
  url = {http://dx.doi.org/10.3389/fcell.2025.1580274},
  DOI = {10.3389/fcell.2025.1580274},
  journal = {Frontiers in Cell and Developmental Biology},
  publisher = {Frontiers Media SA},
  author = {Abu-Sailik,  Fadia and Gariballa,  Nesrin and Ali,  Bassam R.},
  year = {2025},
  month = jun 
}

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