Cystic fibrosis: Carrier screening
- Katharine D Wenstrom, MD
Katharine D Wenstrom, MD
- Professor of Obstetrics and Gynecology
- Alpert School of Medicine at Brown University
Cystic fibrosis (CF) is a life-limiting autosomal recessive disease affecting the airways, pancreas, liver, intestines, sweat glands, and, in males, the vas deferens. It is the most common monogenic disorder in non-Hispanic whites of Northern European descent, with a carrier frequency of 1/24 to 1/25 and birth prevalence of 1 in 2500. Carrier screening is offered to couples planning pregnancy or in early pregnancy to identify those at risk of conceiving a child with classic CF.
This topic will review CF carrier screening and reproductive options for carrier couples, including prenatal diagnosis. Other issues related to CF are discussed separately, including:
CF is caused by mutations in a single large gene on chromosome 7 that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which regulates chloride channel function of epithelial cells of the sweat gland, airway, pancreas, and intestine. Clinical disease occurs when disease-causing mutations are present in both copies of the CFTR gene. Over 1900 different mutations in the CF gene have been identified, although the vast majority of CFTR mutations occur at frequencies less than 1/1000 (<0.1 percent) [1-3]. The specific mutations that an individual carries are a major determinant of clinical severity. The range of clinical expression likely reflects the degree to which protein function is changed by the mutation, modulation of the phenotype by other genes, and variation in susceptibility to environmental factors. (See "Cystic fibrosis: Genetics and pathogenesis".)
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- CF MUTATIONS
- CFTR mutation prevalence
- BENEFITS AND LIMITATIONS OF SCREENING
- CANDIDATES FOR SCREENING
- CARRIER TEST SELECTION
- Standard panel
- Expanded panel
- CFTR sequencing
- SCREENING STRATEGIES
- Couples with no personal or family history of CF
- Couples with a personal or family history of CF
- Father unavailable
- TEST REQUISITION
- TEST PERFORMANCE
- INTERPRETATION OF SCREENING RESULTS
- Positive screen
- Negative screen
- Genetic consultation
- REPRODUCTIVE OPTIONS FOR CARRIER COUPLES
- Noncarrier gamete donor
- Preimplantation genetic diagnosis
- Prenatal diagnosis
- - Chorionic villus sampling and amniocentesis
- - Noninvasive prenatal diagnosis
- - Prediction of phenotype
- PREGNANCY AND PERIPARTUM MANAGEMENT
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS