• 1 Dr. von Hauner Children's Hospital, Department of Pediatrics, University Hospital LMU Munich, Munich, Germany
  • 2 Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
  • 3 Department of Pediatrics, University Malaya Medical Center, Kuala Lumpur, Malaysia
  • 4 Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA
  • 5 Institute of Pathology, Ludwig-Maximilians-Universität München, Munich, Germany
  • 6 Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway
  • 7 Translational Gastroenterology Unit and Department of Pediatrics, University of Oxford, Oxford, UK
  • 8 Department of Biochemistry and Gene Center, Ludwig-Maximilians-Universität München, Munich, Germany
  • 9 SickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada
  • 10 Faculty of Medicine, University of Oslo, Oslo, Norway
  • 11 Dr. von Hauner Children's Hospital, Department of Pediatrics, University Hospital LMU Munich, Munich, Germany.
Nat Genet, 2018 Mar;50(3):344-348.
PMID: 29483653 DOI: 10.1038/s41588-018-0063-6


Transforming growth factor (TGF)-β1 (encoded by TGFB1) is the prototypic member of the TGF-β family of 33 proteins that orchestrate embryogenesis, development and tissue homeostasis1,2. Following its discovery 3 , enormous interest and numerous controversies have emerged about the role of TGF-β in coordinating the balance of pro- and anti-oncogenic properties4,5, pro- and anti-inflammatory effects 6 , or pro- and anti-fibrinogenic characteristics 7 . Here we describe three individuals from two pedigrees with biallelic loss-of-function mutations in the TGFB1 gene who presented with severe infantile inflammatory bowel disease (IBD) and central nervous system (CNS) disease associated with epilepsy, brain atrophy and posterior leukoencephalopathy. The proteins encoded by the mutated TGFB1 alleles were characterized by impaired secretion, function or stability of the TGF-β1-LAP complex, which is suggestive of perturbed bioavailability of TGF-β1. Our study shows that TGF-β1 has a critical and nonredundant role in the development and homeostasis of intestinal immunity and the CNS in humans.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.