title: The Spectrum of CFTR Variants in Nonwhite Cystic Fibrosis Patients: Implications for Molecular Diagnostic Testing.
abstract: Despite the implementation of cystic fibrosis (CF) newborn screening programs across the United States, the identification of CFTR gene variants in nonwhite populations compared with whites remains suboptimal. Our objective was to establish the spectrum of CFTR variants and their frequencies in CF patients in the United States with African, Native American, Asian, East Indian, or Middle Eastern backgrounds. By using direct DNA sequencing, we identified two CFTR variants in 89 of 140 affected nonwhite individuals with uncharacterized genotypes. Seven variants were novel. Multiplex ligation-dependent probe amplification detected 14 rearrangements in the remaining 51 patients, 6 of which were novel. Deletions and duplications accounted for 17% of unidentified alleles. A cross-sectional analysis of genotyping data from the CF Foundation Patient Registry was performed, comparing 3496 nonwhite patients with 22,206 white CF patients. Patients of Hispanic, black, or Asian ancestry were less likely to have two identified CFTR variants (P < 0.0001 for Hispanics and blacks, P = 0.003 for Asians), and more likely to carry no mutations on the commonly used 23 mutation carrier screening panel (P < 0.0001). We analyzed the mutations recorded for each ancestry and summarized the most frequent ones. This research could facilitate equity in mutation detection between white and nonwhite or mixed-ethnicity CF patients, enabling an earlier diagnosis improving their quality of life.
authors.affiliation: Department of Pathology, Stanford University Medical Center, Stanford, California; Department of Pediatrics, Stanford University Medical Center, Stanford, California. Electronic address: ischrijver@stanfordhealthcare.org.
authors.forename: Iris
authors.initials: I
authors.lastname: Schrijver
authors.affiliation: Department of Pathology, Stanford University Medical Center, Stanford, California.
authors.forename: Lynn
authors.initials: L
authors.lastname: Pique
authors.affiliation: Genetic Disease Screening Program, California Department of Public Health, Richmond, California.
authors.forename: Steve
authors.initials: S
authors.lastname: Graham
authors.affiliation: Sequoia Foundation, La Jolla, California.
authors.forename: Michelle
authors.initials: M
authors.lastname: Pearl
authors.affiliation: Department of Pathology, Stanford University Medical Center, Stanford, California; Department of Pediatrics, Stanford University Medical Center, Stanford, California.
authors.forename: Athena
authors.initials: A
authors.lastname: Cherry
authors.affiliation: Environmental Health Investigations Branch, California Department of Public Health, Richmond, California.
authors.forename: Martin
authors.initials: M
authors.lastname: Kharrazi
mesh_terms: D001741:Black or African American / Q000235:genetics; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D003430:Cross-Sectional Studies; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics*; D060005:Genotyping Techniques; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation / Q000235:genetics; D017422:Sequence Analysis, DNA; D014481:United States; D044465:White People / Q000235:genetics
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator