Clinical sensitivity of prenatal screening for cystic fibrosis via CFTR carrier testing in a United States panethnic population.
OBJECTIVE
To estimate CFTR mutation frequencies, clinical sensitivities (proportions of carrier couples or affected fetuses detected), and birth prevalence estimates for broad racial/ethnic groups and for a panethnic U.S. population.


METHODS
Published sources of information were identified, corrected when appropriate, and summarized. Combining racial/ethnic-specific mutation frequencies and birth prevalence estimates allowed the computation of panethnic estimates.


RESULTS
Two of the 25 recommended mutations do not meet the 0.1% threshold in a panethnic population set by the American College of Medical Genetics. The clinical sensitivities are estimated to be 71.9%, 51.7%, 41.6%, 88.6%, and 23.4% for non-Hispanic Caucasians, Hispanic Caucasian, African American, Ashkenazi Jewish Caucasian, and Asian American couples, respectively. Birth prevalence estimates are 1:2,500, 1:13,500, 1:15,100, 1:2,270, and 1:35,100, whereas the number of couples needed to screen to detect an affected fetus are about 3,200, 26,120; 36,040; 2,600, and 129,600, respectively, for the same racial/ethnic groups.


CONCLUSIONS
Overall, the panethnic estimates for CFTR mutation frequencies are similar to those for non-Hispanic Caucasians. However, large differences in both clinical sensitivity and birth prevalence exist between the broad racial/ethnic groups examined. Whether and how the differences in the numbers of couples needed to screen to detect an affected fetus are to be included in prenatal screening for cystic fibrosis needs to be more explicitly addressed.
Palomaki
Glenn E
GE
Foundation for Blood Research, Scarborough, Maine, USA.
FitzSimmons
Stacey C
SC
Haddow
James E
JE
D001741:Black or African American / Q000235:genetics; D001213:Asian / Q000235:genetics; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000453:epidemiology / Q000208:ethnology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005006:Ethnicity; D005260:Female; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D005828:Genetics, Population; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D007585:Jews / Q000235:genetics; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012680:Sensitivity and Specificity; D014481:United States; D044465:White People / Q000235:genetics
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator