title: Diagnostic testing by CFTR gene mutation analysis in a large group of Hispanics: novel mutations and assessment of a population-specific mutation spectrum.
abstract: Characterization of CFTR mutations in the U.S. Hispanic population is vital to early diagnosis, genetic counseling, patient-specific treatment, and the understanding of cystic fibrosis (CF) pathogenesis. The mutation spectrum in Hispanics, however, remains poorly defined. A group of 257 self-identified Hispanics with clinical manifestations consistent with CF were studied by temporal temperature gradient electrophoresis and/or DNA sequencing. A total of 183 mutations were identified, including 14 different amino acid-changing novel variants. A significant proportion (78/85) of the different mutations identified would not have been detected by the ACMG/ACOG-recommended 25-mutation screening panel. Over one third of the mutations (27/85) occurred with a relative frequency >1%, which illustrates that the identified mutations are not all rare. This is supported by a comparison with other large CFTR studies. These results underscore the disparity in mutation identification between Caucasians and Hispanics and show utility for comprehensive diagnostic CFTR mutation analysis in this population.
authors.affiliation: Department of Pathology, L235, Stanford University Medical Center, Stanford, CA 94305, USA. iris.schrijver@medcenter.stanford.edu
authors.forename: Iris
authors.initials: I
authors.lastname: Schrijver
authors.forename: Sudha
authors.initials: S
authors.lastname: Ramalingam
authors.forename: Ramalingam
authors.initials: R
authors.lastname: Sankaran
authors.forename: Steve
authors.initials: S
authors.lastname: Swanson
authors.forename: Charles L M
authors.initials: CL
authors.lastname: Dunlop
authors.forename: Steven
authors.initials: S
authors.lastname: Keiles
authors.forename: Richard B
authors.initials: RB
authors.lastname: Moss
authors.forename: John
authors.initials: J
authors.lastname: Oehlert
authors.forename: Phyllis
authors.initials: P
authors.lastname: Gardner
authors.forename: E Robert
authors.initials: ER
authors.lastname: Wassman
authors.forename: Anja
authors.initials: A
authors.lastname: Kammesheidt
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000208:ethnology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D042241:Early Diagnosis; D005260:Female; D005787:Gene Frequency; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator