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, 312O+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.