title: Molecular genetic testing for cystic fibrosis: laboratory performance on the College of American Pathologists external proficiency surveys.
abstract: BACKGROUND
  Molecular testing for cystic fibrosis mutations is widespread and routine in reproductive decision making and diagnosis. Our objective was to assess the level of performance of laboratories for this test.
  
  
  METHODS
  The College of American Pathologists administers external proficiency testing with multiple DNA samples distributed biannually. RESULTS are analyzed, reviewed, and graded by the joint College of American Pathologists/American College of Medical Genetics and Genomics Biochemical and Molecular Genetics Committee. Assessment is based on genotype and associated clinical interpretation.
  
  
  RESULTS
  Overall, 357 clinical laboratories participated in the proficiency testing survey between 2003 and 2013 (322 in the United States and 35 international). In 2013, US participants reported performing nearly 120,000 tests monthly. Analytical sensitivity and specificity of US laboratories were 98.8% (95% confidence interval: 98.4-99.1%) and 99.6% (95% confidence interval: 99.4-99.7%), respectively. Analytical sensitivity improved between 2003 and 2008 (from 97.9 to 99.3%; P = 0.007) and remained steady thereafter. Clinical interpretation matched the intended response for 98.8, 86.0, and 91.0% of challenges with no, one, or two mutations, respectively. International laboratories performed similarly.
  
  
  CONCLUSIONS
  Laboratory testing for cystic fibrosis in the United States has improved since 2003, and these data demonstrate a high level of quality. Neither the number of samples tested nor test methodology affected performance.
authors: 1] Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah, USA [2] ARUP Laboratories, Salt Lake City, Utah, USA.
authors: Elaine
authors: E
authors: Lyon
authors: 1] Department of Pathology, School of Medicine, Stanford University, Stanford, California, USA [2] Department of Pediatrics, School of Medicine, Stanford University, Stanford, California, USA.
authors: Iris
authors: I
authors: Schrijver
authors: 1] Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA [2] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors: Karen E
authors: KE
authors: Weck
authors: Department of Pathology, Virginia Commonwealth University, Richmond, Virginia, USA.
authors: Andrea
authors: A
authors: Ferreira-Gonzalez
authors: Knight Diagnostic Laboratories, Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, Oregon, USA.
authors: C Sue
authors: CS
authors: Richards
authors: Department of Pathology and Laboratory Medicine, Women & Infants Hospital, Alpert Medical School, Brown University, Providence, Rhode Island, USA.
authors: Glenn E
authors: GE
authors: Palomaki
mesh_terms: D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D003625:Data Collection; D005820:Genetic Testing / Q000379:methods* / Q000592:standards; D006801:Humans; D007753:Laboratories / Q000592:standards*; D059021:Laboratory Proficiency Testing; D009154:Mutation; D012955:Societies, Medical; D014481:United States
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator