title: The c.1364C>A (p.A455E) Mutation in the CFTR Pseudogene Results in an Incorrectly Assigned Carrier Status by a Commonly Used Screening Platform.
abstract: Cystic fibrosis (CF) is one of the most common recessive conditions among whites, with an estimated carrier frequency of 1 in 25 in the United States. Population-based CF carrier screening was implemented in the United States in 2001. The number of mutations screened by each laboratory may vary; however, the 23 most common CF mutations recommended for screening by the American College of Medical Genetics and American College of Obstetricians and Gynecologists are included in all platforms. The c.1364C>A (p.A455E) mutation located in exon 10 of the CFTR gene is one of the 23 mutations. Because CFTR exon 10 and its flanking intronic regions are duplicated and transposed onto several other chromosomes of the human genome during evolution and function as unprocessed pseudogenes, variations in the CFTR pseudogenes may confound CF screening results for mutations located in exon 10 of the CFTR gene. We report an incorrectly identified carrier status for the c.1364C>A (p.A455E) mutation in a healthy individual using the Hologic InPlex CF assay. Further analysis revealed that the mutation resides in one of the CFTR pseudogenes. Because most commercial kits and laboratory-developed tests for CF carrier screening involve a short amplicon encompassing this mutation, this finding suggests that individuals with the c.1364C>A (p.A455E) mutation may require further investigation to avoid a false assignment of CF carrier status.
authors.affiliation: Center for Human Genetics Laboratory, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Kristin K
authors.initials: KK
authors.lastname: Deeb
authors.affiliation: Center for Human Genetics Laboratory, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: James D
authors.initials: JD
authors.lastname: Metcalf
authors.affiliation: Center for Human Genetics Laboratory, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Kaitlin M
authors.initials: KM
authors.lastname: Sesock
authors.affiliation: Center for Human Genetics Laboratory, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Junqing
authors.initials: J
authors.lastname: Shen
authors.affiliation: Center for Human Genetics Laboratory, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Wensel
authors.affiliation: Department of Pathology, Center for Human Genetics, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Larisa I
authors.initials: LI
authors.lastname: Rippel
authors.affiliation: Center for Human Genetics Laboratory, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Michelle
authors.initials: M
authors.lastname: Smith
authors.affiliation: Department of Obstetrics and Gynecology, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Chapman
authors.affiliation: Center for Human Genetics Laboratory, University Hospitals Case Medical Center, Cleveland, Ohio. Electronic address: shulin.zhang@uhhospitals.org.
authors.forename: Shulin
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000328:Adult; D001483:Base Sequence; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005820:Genetic Testing / Q000379:methods; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D011544:Pseudogenes / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D014481:United States
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator