title: Increased Prevalence of Inflammatory Bowel Disease in Patients with Mutations in Genes Encoding the Receptor Subunits for TGFβ.
abstract: TGFβ is a multifunctional cytokine that is critical in regulating mucosal immunity. Murine studies have revealed that disruption of canonical TGFβ signaling leads to systemic inflammation including colitis. Loeys-Dietz syndrome (LDS) results from heterozygous mutations in the genes encoding the subunits of the TGFβ receptor.
  
  
  
  All patients with confirmed mutations in TGFBR1 or TGFBR2, seen in the Johns Hopkins Connective Tissue Disorders clinic, were asked to participate in the study. Ninety-three consecutive patients were enrolled, including 4 with inflammatory bowel disease (IBD). Using the Illumina Immunochip array, we undertook an exploratory analysis to evaluate the potential genetic risk factors that could predict which patients with LDS would develop IBD.
  
  
  
  We report an increased prevalence of IBD in patients with LDS types I and II. We describe the course of several patients. In this small sample, the 3 whites with IBD had a genetic risk score in the top 6 highest scores of patients evaluated.
  
  
  
  We report a 10-fold increase in the prevalence of IBD in patients with LDS compared with the general population. Onset of disease in 3 of the 4 patients was at less than 18 years, and the clinical course in 2 of the 4 was severe with a poor response to traditional medications. Further evaluation of the genetic risk score is needed to determine whether it can predict which patients with LDS are most likely to develop IBD. This case series of patients with LDS with IBD suggests that defective TGFβ signaling may have an influence on IBD risk.
authors: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors: Anthony L
authors: AL
authors: Guerrerio
authors: Division of Intramural Research, NIAID, NIH.
authors: Pamela A
authors: PA
authors: Frischmeyer-Guerrerio
authors: Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, Johns Hopkins University School of Medicine, and Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
authors: Chengrui
authors: C
authors: Huang
authors: Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, Johns Hopkins University School of Medicine, and Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
authors: Yuqiong
authors: Y
authors: Wu
authors: The F.Widjaja Foundation Inflammatory Bowel and Immunology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors: Talin
authors: T
authors: Haritunians
authors: The F.Widjaja Foundation Inflammatory Bowel and Immunology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors: Dermot P B
authors: DPB
authors: McGovern
authors: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors: Gretchen L
authors: GL
authors: MacCarrick
authors: Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, Johns Hopkins University School of Medicine, and Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
authors: Steven R
authors: SR
authors: Brant
authors: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.|Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors: Harry C
authors: HC
authors: Dietz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D015212:Inflammatory Bowel Diseases / Q000453:epidemiology*; D055947:Loeys-Dietz Syndrome / Q000150:complications* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014481:United States; D055815:Young Adult
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625841:TGFBR1 protein, human