Cystic fibrosisis a common autosomal recessive genetic disorder with an incidence of approximately 1:3000 births. Over 1000 mutations in the cystic fibrosis transmembrane regulator (CFTR) gene have been described.
JMMC Clinical Laboratory offers a Cystic Fibrosis Mutation screening test that includes all core mutations recommended by the American College of Obstetricians and Gynecologists (ACOG) and the American College of Medical Genetics (ACMG) for population-based CF carrier screening. While some assay platforms may detect rare mutations not included in the standard ACOG/ACMG panel, these mutations are not reported due to lack of consensus by ACOG/ACMG.
A negative test result does not rule out cystic fibrosis disease or carrier status. The risk for mutations other than the ones tested depends greatly on family and clinical history as well as ethnicity. If an individual is asymptomatic and has no family history of cystic fibrosis, the following table is valid for deteminiing their residual risk to carry a CF mutation.
|Ethnic Group||Detection Rate||Estimated Carrier Risk Prior to Testing
||Estimated Carrier Risk after Negative Test|
|Ashkenazi Jew||97%||1/25||1 in 830|
|European Caucasian||90%||1/25||1 in 250|
|African American||69%||1/65||1 in 207|
|Hispanic American||57%||1/46||1 in 105|
A heterozygous positive result indicates that an individual is at least a carrier for cystic fibrosis. Carrier status assumes that this individual is not clinically affected. If cystic fibrosis is suspected, the individual may have a second mutation not detected by this assay, and testing for additional mutations is recommended. Genetic counseling and additional testing by mutation analysis should be offered to patients, relatives and reproductive partners.
A homozygous positive result indicates that an individual is affected with cystic fibrosis. Genetic counseling and additional testing by mutation analysis for the patient and family members is recommended.
These mutations are detected by linear signal amplification developed by Invader® DNA Technology. The method employs a novel, homogeneous platform that analyzes DNA without prior amplification of the target. The assay uses Cleavase® enzymes to recognize and cleave specific structures formed by the addition of two oligonucleotides to a nucleic acid target. The signals generated in the reaction are detected by a fluorescent microtiter plate reader.
The performance characteristics of this test were validated by John Muir Medical Center Clinical Laboratories. The U.S. Food and Drug Administration (FDA) has not approved this test. However, FDA approval is currently not required for clinical use of this test. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions. This test is performed pursuant to an agreement with Third Wave Techolgies.