title: Does extensive genotyping and nasal potential difference testing clarify the diagnosis of cystic fibrosis among patients with single-organ manifestations of cystic fibrosis?
abstract: BACKGROUND
  The phenotypic spectrum of cystic fibrosis (CF) has expanded to include patients affected by single-organ diseases. Extensive genotyping and nasal potential difference (NPD) testing have been proposed to assist in the diagnosis of CF when sweat testing is inconclusive. However, the diagnostic yield of extensive genotyping and NPD and the concordance between NPD and the sweat test have not been carefully evaluated.
  
  
  METHODS
  We evaluated the diagnostic outcomes of genotyping (with 122 mutations included as disease causing), sweat testing and NPD in a prospectively ascertained cohort of undiagnosed patients who presented with chronic sino-pulmonary disease (RESP), chronic/recurrent pancreatitis (PANC) or obstructive azoospermia (AZOOSP).
  
  
  RESULTS
  202 patients (68 RESP, 42 PANC and 92 AZOOSP) were evaluated; 17.3%, 22.8% and 59.9% had abnormal, borderline and normal sweat chloride results, respectively. Only 17 (8.4%) patients were diagnosable as having CF by genotyping. Compared to sweat testing, NPD identified more patients as having CF (33.2%) with fewer borderline results (18.8%). The level of agreement according to kappa statistics (and the observed percentage of agreement) between sweat chloride and NPD in RESP, PANC and AZOOSP subjects was 'moderate' (65% observed agreement), 'poor' (33% observed agreement) and 'fair' (28% observed agreement), respectively. The degree of agreement only improved marginally when subjects with borderline sweat chloride results were excluded from the analysis.
  
  
  CONCLUSIONS
  The diagnosis of CF or its exclusion is not always straightforward and may remain elusive even with comprehensive evaluation, particularly among individuals who present at an older age with single-organ manifestations suggestive of CF.
authors.affiliation: Physiology and Experimental Medicine, Research Institute, The Hospital for Sick Children, , Toronto, Canada.
authors.forename: Chee Y
authors.initials: CY
authors.lastname: Ooi
authors.forename: Annie
authors.initials: A
authors.lastname: Dupuis
authors.forename: Lynda
authors.initials: L
authors.lastname: Ellis
authors.forename: Keith
authors.initials: K
authors.lastname: Jarvi
authors.forename: Sheelagh
authors.initials: S
authors.lastname: Martin
authors.forename: Peter N
authors.initials: PN
authors.lastname: Ray
authors.forename: Leslie
authors.initials: L
authors.lastname: Steele
authors.forename: Paul
authors.initials: P
authors.lastname: Kortan
authors.forename: Tanja
authors.initials: T
authors.lastname: Gonska
authors.forename: Ruslan
authors.initials: R
authors.lastname: Dorfman
authors.forename: Melinda
authors.initials: M
authors.lastname: Solomon
authors.forename: Julian
authors.initials: J
authors.lastname: Zielenski
authors.forename: Mary
authors.initials: M
authors.lastname: Corey
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tullis
authors.forename: Peter
authors.initials: P
authors.lastname: Durie
mesh_terms: D000328:Adult; D000483:Alleles; D015415:Biomarkers / Q000378:metabolism; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009297:Nasal Mucosa / Q000378:metabolism*; D010641:Phenotype; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012965:Sodium Chloride / Q000378:metabolism*; D013542:Sweat / Q000378:metabolism
chemical_list: D015415:Biomarkers; C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012965:Sodium Chloride
keywords: Bronchiectasis; Cystic Fibrosis; Paediatric Lung Disaese