title: Evaluation of a BeadXpress assay for a 151-mutation and variant CFTR screening panel after 11,000 samples: implications for practice.
abstract: We created a 151-mutation and variant screening panel for cystic fibrosis transmembrane regulator (CFTR) using the Illumina Inc. BeadXpress platform (San Diego, CA). The laboratory developed test was validated using a third-party blinding of a set of 450 samples split with an authority laboratory that provides a large panel CFTR screening and 50 diverse controls admixed randomly. The validation proved the test to be 100% sensitive for the mutations tested and >99% specific. A total of 391 mutations in 11,186 samples tested were confirmed by repeat analysis and sequencing, resulting in an overall confirmed positive rate of 3.5%. Of the mutations detected, 348 were part of the American College of Obstetrics and Gynecology (ACOG) panel (89%) and 43 were non-ACOG (11%). A total of 16 of the 23 ACOG panel mutations were discovered in this cohort, along with 21 different non-ACOG mutation genotypes. We confirmed 6 total patients carrying mutations that would not have been identified by any other commercial panel. The role of a large genotyping panel in carrier screening is discussed relative to the ACOG panel and also in relation to comparative efficacy with targeted massive parallel sequencing.
authors.affiliation: aMDx Laboratory Sciences, Ann Arbor, MI 48103, USA. jay.stoerker@amdxlabs.com
authors.forename: Jay
authors.initials: J
authors.lastname: Stoerker
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Goodman
authors.forename: Heather M
authors.initials: HM
authors.lastname: Walline
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Sugalski
authors.forename: Carol A
authors.initials: CA
authors.lastname: Holland
mesh_terms: D003550:Cystic Fibrosis / Q000175:diagnosis*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods*; D005838:Genotype; D006801:Humans; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D050505:Mutant Proteins / Q000235:genetics; D012680:Sensitivity and Specificity
chemical_list: C505032:CFTR protein, human; D050505:Mutant Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator