title: Primary sclerosing cholangitis in childhood is associated with abnormalities in cystic fibrosis-mediated chloride channel function.
abstract: OBJECTIVE
  To determine whether primary sclerosing cholangitis (PSC) in childhood is associated with abnormalities in cystic fibrosis transmembrane conductance regulator (CFTR).
  
  
  METHODS
  Subjects with PSC diagnosed in childhood (n = 20) were recruited from Children's Hospital. Subjects had testing with sweat chloride concentration, nasal transmembrane potential difference, and extensive genetic analysis of the CFTR gene. Disease control subjects consisted of 14 patients with inflammatory bowel disease alone and no liver disease. t tests were performed to determine statistical significance.
  
  
  RESULTS
  In the PSC group, CFTR chloride channel function (deltaChloride free + isoproterenol) was markedly diminished at -8.6 +/- 8.2 mV (reference range: -24.6 +/- 10.4 mV). In contrast, disease control subjects had normal function, at -17.8 +/- 9.7 mV (P = .008). Sweat chloride concentration in subjects with PSC was greater than in disease control subjects (20.8 +/- 3.4 mmol/L vs 12.0 +/- 1.6 mmol/L, P = .045). Comprehensive CFTR genotyping revealed that 5 of 19 (26.3%) subjects with PSC had a CFTR mutation or variant, compared with 6 of 14 (42.9%) disease control subjects.
  
  
  CONCLUSIONS
  There is a high prevalence of CFTR-mediated ion transport dysfunction in subjects with childhood PSC.
authors.affiliation: Division of Pediatric Gastroenterology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA. harpreet.pall@childrens.harvard.edu
authors.forename: Harpreet
authors.initials: H
authors.lastname: Pall
authors.forename: Julian
authors.initials: J
authors.lastname: Zielenski
authors.forename: Maureen M
authors.initials: MM
authors.lastname: Jonas
authors.forename: Deborah A
authors.initials: DA
authors.lastname: DaSilva
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Potvin
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Yuan
authors.forename: Qiuju
authors.initials: Q
authors.lastname: Huang
authors.forename: Steven D
authors.initials: SD
authors.lastname: Freedman
mesh_terms: D000293:Adolescent; D002760:Cholangiopancreatography, Endoscopic Retrograde; D049448:Cholangiopancreatography, Magnetic Resonance; D015209:Cholangitis, Sclerosing / Q000175:diagnosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D017136:Ion Transport / Q000235:genetics; D007545:Isoproterenol / Q000097:blood; D008297:Male; D047492:Peroxisome Proliferator-Activated Receptors / Q000502:physiology; D011446:Prospective Studies; D013542:Sweat / Q000737:chemistry
chemical_list: D047492:Peroxisome Proliferator-Activated Receptors; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D007545:Isoproterenol