Cystic fibrosis testing 8 years on: lessons learned from carrier screening and sequencing analysis.
OBJECTIVE
This study reviews data from our cystic fibrosis testing program to evaluate the performance of population-based carrier screening and compare observed detection rates with predicted results of the American College of Medical Genetics/American College of Obstetricians and Gynecologists recommended panel of 23 mutations.


METHODS
We queried our proprietary databases containing approximately 3 million cystic fibrosis screening tests, 1300 prenatal diagnostic tests, and 2400 cystic fibrosis sequencing analyses.


RESULTS
We observed an overall cystic fibrosis carrier frequency of 1:37.6 individuals in the pan-ethnic tested population. This represents a detection rate of 77%, given an estimated US pan-ethnic carrier frequency of 1:29. For patients self-identified as white or Ashkenazi Jewish, a carrier frequency of 1:29 and 1:27 were observed, respectively. A combined frequency of 1:28, representing close to 90% of carriers, was identified in these two highest risk populations. In total, 119 affected fetuses were identified by prenatal diagnoses, a ratio of 1 affected fetus per 25,000 carrier screens. Of 62 newborns with positive immunoreactive trypsinogen and positive sweat tests, almost all of whom had been tested using the American College of Medical Genetics/American College of Obstetricians and Gynecologists panel, only two individuals would have been identified using an expanded mutation panel.


CONCLUSIONS
The American College of Medical Genetics/American College of Obstetricians and Gynecologists panel of 23 mutations is performing as predicted in detecting cystic fibrosis carriers in the United States among all ethnic groups. No recurrent mutations have been detected in sufficient numbers to justify including any additional mutations to the existing panel. An expanded American College of Medical Genetics/American College of Obstetricians and Gynecologists panel would have a minimal impact on the prevention of births of children affected with cystic fibrosis.
Nichols Institute, Quest Diagnostics, Genetic Testing Center, 33608 Ortega Highway, San Juan Capistrano, San Juan Capistrano, California 92675-2042, USA. charles.m.strom@questdiagnostics.com
Charles M
CM
Strom
Beryl
B
Crossley
Arlene
A
Buller-Buerkle
Michael
M
Jarvis
Franklin
F
Quan
Mei
M
Peng
Kasinathan
K
Muralidharan
Victoria
V
Pratt
Joy B
JB
Redman
Weimin
W
Sun
D002648:Child; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D006580:Genetic Carrier Screening / Q000379:methods*; D005820:Genetic Testing / Q000379:methods*; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D015995:Prevalence; D044469:Racial Groups / Q000235:genetics; D014481:United States / Q000453:epidemiology / Q000208:ethnology