title: Identification of novel and rare mutations in California Hispanic and African American cystic fibrosis patients.
abstract: In ethnic heterogeneous California, complete genetic information is currently lacking to build solid population-based cystic fibrosis (CF) screening programs because a large proportion of mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR/ABCC7) are still unknown, especially in non-Caucasian patients. A total of 402 [46 African American+356 Hispanic] Hispanic and African American patients from California CF patient registry were included in this study. Patients with at least one unidentified mutant allele were asked to donate blood samples for further analysis, first by Genzyme Genetics for a panel of 87 known mutations, followed by temporal temperature gradient gel electrophoresis (TTGE) scanning of the entire coding exons of CFTR gene. A total of eight novel mutations; one missense mutation, one splice-site mutation and six frame-shift mutations were identified. In addition to the eight novel mutations, 20 [corrected] distinct rare mutations that are not in the current available commercial mutation panels were identified by TTGE. The overall detection rate was raised to 95.7% for African American and 94.5% for Hispanic. The discovery of recurrent rare and novel mutations improves the diagnosis and care of persons with CF and improves our ability to adequately and equitably provide screening and genetic counseling services to non-Caucasians.
authors.affiliation: Institute for Molecular and Human Genetics, Georgetown University Medical Center, Washington, DC 20007-2113, USA.
authors.forename: Ozgül M
authors.initials: OM
authors.lastname: Alper
authors.forename: Lee-Jun C
authors.initials: LJ
authors.lastname: Wong
authors.forename: Suzanne
authors.initials: S
authors.lastname: Young
authors.forename: Michelle
authors.initials: M
authors.lastname: Pearl
authors.forename: Steve
authors.initials: S
authors.lastname: Graham
authors.forename: John
authors.initials: J
authors.lastname: Sherwin
authors.forename: Eliezer
authors.initials: E
authors.lastname: Nussbaum
authors.forename: Dennis
authors.initials: D
authors.lastname: Nielson
authors.forename: Arnold
authors.initials: A
authors.lastname: Platzker
authors.forename: Zoe
authors.initials: Z
authors.lastname: Davies
authors.forename: Allan
authors.initials: A
authors.lastname: Lieberthal
authors.forename: Terry
authors.initials: T
authors.lastname: Chin
authors.forename: Greg
authors.initials: G
authors.lastname: Shay
authors.forename: Karen
authors.initials: K
authors.lastname: Hardy
authors.forename: Martin
authors.initials: M
authors.lastname: Kharrazi
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D002140:California / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000208:ethnology* / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D016368:Frameshift Mutation; D005817:Genetic Counseling; D005820:Genetic Testing; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D022821:RNA Splice Sites / Q000235:genetics; D013696:Temperature
chemical_list: C505032:CFTR protein, human; D022821:RNA Splice Sites; D019005:Cystic Fibrosis Transmembrane Conductance Regulator