Analytic validity of cystic fibrosis testing: a preliminary estimate.
OBJECTIVE
Derive estimates of analytic sensitivity and specificity of DNA testing for cystic fibrosis in the United States.


METHODS
Analyze published results of the American College of Medical Genetics (ACMG)/College of American Pathologists (CAP) Molecular Genetics Survey between 1996 and 2001, taking into account difficult, simulated clinical samples included for educational purposes.


RESULTS
Analytic sensitivity is 97.9% [95% confidence interval (CI) 96.8-98.7%], and analytic specificity is 99.4% (95% CI 98.7-99.9%) after removing challenges involving delI507 and performing other adjustments. Analytic sensitivity is consistent over the 6 years. Specificity was lower in 1997.


CONCLUSIONS
These preliminary estimates indicate that analytic validity of cystic fibrosis testing is very good and can likely be improved. To date, fewer than half of the mutations in the panel recommended for preconceptional or prenatal screening have been challenged. The present study highlights the value of performing confirmatory testing when a mutation is identified to reduce false-positive results.
Palomaki
Glenn E
GE
Foundation for Blood Research, Scarborough, Maine 04070-0190, USA.
Bradley
Linda A
LA
Richards
C Sue
CS
Haddow
James E
JE
D000483:Alleles; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000235:genetics; D004252:DNA Mutational Analysis; D003625:Data Collection; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008403:Mass Screening; D012680:Sensitivity and Specificity