title: Clinical Sensitivity of Cystic Fibrosis Mutation Panels in a Diverse Population.
abstract: Infants are screened for cystic fibrosis (CF) in New York State (NYS) using an IRT-DNA algorithm. The purpose of this study was to validate and assess clinical validity of the US FDA-cleared Illumina MiSeqDx CF 139-Variant Assay (139-VA) in the diverse NYS CF population. The study included 439 infants with CF identified via newborn screening (NBS) from 2002 to 2012. All had been screened using the Abbott Molecular CF Genotyping Assay or the Hologic InPlex CF Molecular Test. All with CF and zero or one mutation were tested using the 139-VA. DNA extracted from dried blood spots was reliably and accurately genotyped using the 139-VA. Sixty-three additional mutations were identified. Clinical sensitivity of three panels ranged from 76.2% (23 mutations recommended for screening by ACMG/ACOG) to 79.7% (current NYS 39-mutation InPlex panel), up to 86.0% for the 139-VA. For all, sensitivity was highest in Whites and lowest in the Black population. Although the sample size was small, there was a nearly 20% increase in sensitivity for the Black CF population using the 139-VA (68.2%) over the ACMG/ACOG and InPlex panels (both 50.0%). Overall, the 139-VA is more sensitive than other commercially available panels, and could be considered for NBS, clinical, or research laboratories conducting CF screening.
authors.affiliation: Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Hughes
authors.affiliation: Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York.
authors.forename: Colleen F
authors.initials: CF
authors.lastname: Stevens
authors.affiliation: Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Saavedra-Matiz
authors.affiliation: Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York.|Department of Biomedical Sciences, School of Public Health, State University of New York, Albany, New York.
authors.forename: Norma P
authors.initials: NP
authors.lastname: Tavakoli
authors.affiliation: Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York.
authors.forename: Lea M
authors.initials: LM
authors.lastname: Krein
authors.affiliation: Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York.
authors.forename: April
authors.initials: A
authors.lastname: Parker
authors.affiliation: Applied Genomics Technologies Core, Wadsworth Center, New York State Department of Health, Albany, New York.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York.
authors.forename: Breanne
authors.initials: B
authors.lastname: Maloney
authors.affiliation: Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York.
authors.forename: Beth
authors.initials: B
authors.lastname: Vogel
authors.affiliation: Cohen Children's Medical Center of New York, Great Neck, New York.
authors.forename: Joan
authors.initials: J
authors.lastname: DeCelie-Germana
authors.affiliation: University Medical Center at Stony Brook, Stony Brook, New York.
authors.forename: Catherine
authors.initials: C
authors.lastname: Kier
authors.affiliation: SUNY Upstate Medical University/Golisano Children's Hospital, Syracuse, New York.
authors.forename: Ran D
authors.initials: RD
authors.lastname: Anbar
authors.affiliation: The Cystic Fibrosis Center, Mount Sinai Beth Israel, New York, New York.
authors.forename: Maria N
authors.initials: MN
authors.lastname: Berdella
authors.affiliation: Albany Medical Center, Albany, New York.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Comber
authors.affiliation: Maria Fareri Children's Hospital at Westchester Medical Center and New York Medical College, Valhalla, New York.
authors.forename: Allen J
authors.initials: AJ
authors.lastname: Dozor
authors.affiliation: Women & Children's Hospital of Buffalo, Buffalo, New York.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Goetz
authors.affiliation: Good Samaritan Hospital, North Babylon, New York.
authors.forename: Louis
authors.initials: L
authors.lastname: Guida
authors.affiliation: Columbia University Medical Center, New York, New York.
authors.forename: Meyer
authors.initials: M
authors.lastname: Kattan
authors.affiliation: Mount Sinai School of Medicine, New York, New York.
authors.forename: Andrew
authors.initials: A
authors.lastname: Ting
authors.affiliation: Strong Memorial Hospital, University of Rochester Medical Center, Rochester, New York.
authors.forename: Karen Z
authors.initials: KZ
authors.lastname: Voter
authors.affiliation: Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York.|Applied Genomics Technologies Core, Wadsworth Center, New York State Department of Health, Albany, New York.
authors.forename: Patrick
authors.initials: P
authors.lastname: van Roey
authors.affiliation: Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York.
authors.forename: Michele
authors.initials: M
authors.lastname: Caggana
authors.affiliation: Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Kay
mesh_terms: D001681:Biological Assay; D044383:Black People; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D059788:Dried Blood Spot Testing; D005260:Female; D005820:Genetic Testing; D060005:Genotyping Techniques; D006630:Hispanic or Latino; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D015997:Neonatal Screening; D012680:Sensitivity and Specificity; D044465:White People
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: CFTR; NGS; clinical sensitivity; cystic fibrosis; mutation panel; newborn screening; next-generation sequencing