title: Identification of common cystic fibrosis mutations in African-Americans with cystic fibrosis increases the detection rate to 75%.
abstract: Cystic fibrosis (CF)--an autosomal recessive disorder caused by mutations in CF transmembrane conductance regulator (CFTR) and characterized by abnormal chloride conduction across epithelial membranes, leading to chronic lung and exocrine pancreatic disease--is less common in African-Americans than in Caucasians. No large-scale studies of mutation identification and screening in African-American CF patients have been reported, to date. In this study, the entire coding and flanking intronic sequence of the CFTR gene was analyzed by denaturing gradient-gel electrophoresis and sequencing in an index group of 82 African-American CF chromosomes to identify mutations. One novel mutation, 3120+1G-->A, occurred with a frequency of 12.3% and was also detected in a native African patient. To establish frequencies, an additional group of 66 African-American CF chromosomes were screened for mutations identified in two or more African-American patients. Screening for 16 "common Caucasian" mutations identified 52% of CF alleles in African-Americans, while screening for 8 "common African" mutations accounted for an additional 23%. The combined detection rate of 75% was comparable to the sensitivity of mutation analysis in Caucasian CF patients. These results indicate that African-Americans have their own set of "common" CF mutations that originate from the native African population. Inclusion of these "common" mutations substantially improves CF mutation detection rates in African-Americans.
authors.affiliation: Department of Pediatrics and Center for Medical Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21287-3914, USA.
authors.forename: M
authors.initials: M
authors.lastname: Macek
authors.forename: A
authors.initials: A
authors.lastname: Mackova
authors.forename: A
authors.initials: A
authors.lastname: Hamosh
authors.forename: B C
authors.initials: BC
authors.lastname: Hilman
authors.forename: R F
authors.initials: RF
authors.lastname: Selden
authors.forename: G
authors.initials: G
authors.lastname: Lucotte
authors.forename: K J
authors.initials: KJ
authors.lastname: Friedman
authors.forename: M R
authors.initials: MR
authors.lastname: Knowles
authors.forename: B J
authors.initials: BJ
authors.lastname: Rosenstein
authors.forename: G R
authors.initials: GR
authors.lastname: Cutting
mesh_terms: D000293:Adolescent; D000328:Adult; D000349:Africa; D044383:Black People / Q000235:genetics*; D018388:Codon, Terminator; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D016368:Frameshift Mutation; D005820:Genetic Testing; D006801:Humans; D008297:Male; D009154:Mutation; D017354:Point Mutation; D014481:United States; D001741:Black or African American
chemical_list: C505032:CFTR protein, human; D018388:Codon, Terminator; D019005:Cystic Fibrosis Transmembrane Conductance Regulator