Laboratory standards and guidelines for population-based cystic fibrosis carrier screening.

In 1997, the National Institutes of Health convened a Consensus Development Conference on Cystic Fibrosis (CF).1 The Consensus Conference recommended that genetic screening for CF mutations should be offered to identify carriers among adults with a positive family history of CF, partners of individuals with CF, couples currently planning a pregnancy, and couples seeking prenatal care. A second NIH-sponsored conference that focused on the implementation of the Consensus Conference recommendations was held in 1998.2 Shortly thereafter, the American College of Medical Genetics (ACMG) and the American College of Obstetricians and Gynecologists (ACOG), in conjunction with the National Human Genome Research Institute, formed a Steering Committee to coordinate the implementation of population-based CF carrier screening and to develop “Clinical and Laboratory Provider Guidelines” for (1) provider education; (2) laboratory testing, interpretation, and genetic counseling; and (3) patient education and informed consent. The ACMG charged the Accreditation of Genetic Services Committee, chaired by Dr. Robert Desnick, to establish a Subcommittee on Cystic Fibrosis Carrier Screening (henceforth the “Committee”) to develop recommendations and guidelines for optimal laboratory testing, interpretation, and counseling. The Subcommittee, cochaired by Drs. Wayne Grody and Garry Cutting, met twice yearly since October 1998. The issues considered by the Committee included (1) the target population to be screened (universal vs. limited to certain high-risk ethnic groups); (2) the screening model to be used (couple-based vs. sequential); (3) criteria for and selection of the standard mutation testing panel; (4) potential value and use of an extended testing panel with additional mutations; (5) whether to test for mutations and variants associated with mild or nonclassical phenotypes (such as congenital bilateral absence of the vas deferens); (6) test interpretation, reporting, and genetic counseling; and (7) laboratory quality assurance. The recommendations detailed here have been incorporated into a joint ACMG/ACOG/NIH Steering Committee document entitled “Preconceptual and Prenatal Carrier Screening for Cystic Fibrosis” which will be widely distributed. This document also will include guidelines for providers, patient education, and informed consent. Patient education materials will include two pamphlets, entitled “Cystic Fibrosis Carrier Testing. . . The Decision is Yours” and “Cystic Fibrosis Testing: What Happens if Both My Partner and I are Carriers?” It is important to note that these guidelines were prepared for population CF carrier screening and that different testing and counseling strategies would be employed for the identification of the mutation(s) in patients diagnosed with CF or in relatives of CF patients. Such diagnostic and prenatal mutation analyses should be referred to a genetics center for appropriate testing and counseling.