Objective: To review the current status of scientific knowledge and opinion regarding molecular genetic testing of mutations in the CFTR gene for purposes of diagnosis and population carrier screening of cystic fibrosis (CF).
Data sources: Published research findings on the nature of the CFTR gene, pilot population screening studies in the United States and Europe, and ongoing deliberations of professional and governmental agencies considering implementation of widespread testing.
Study selection: Findings relevant to the molecular heterogeneity of CFTR mutations and its implications for population carrier screening were considered.
Data extraction: Information was extracted from studies published by us and others, as made available to recent consensus panels and professional committees.
Data synthesis: These data were reevaluated in light of recent movements in professional and public policy regarding acceptability and desirability of widespread CF mutation testing. Effects to date of such testing on patient outcomes is reported.
Conclusions: The ability to test for CFTR mutations at the molecular level has already improved the diagnosis of symptomatic patients and expanded the reproductive options of family members of CF patients. The same technology also holds promise of identifying asymptomatic carriers and at-risk couples without family history in the general population so that they too might be offered prenatal diagnosis or other options. However, a number of key questions remain to be worked out before a widespread national screening program can be put into practice. These include the target population to be offered testing (the entire population vs high-risk ethnic groups), the size and nature of the mutation test panel (universal vs ethnic specific), the inclusion or exclusion of CFTR variants that do not cause classical CF, the optimal testing technology, appropriate standards for laboratory quality assurance, and the development of sufficient educational materials and genetic counseling resources for test delivery, reporting, and interpretation. The answers to these questions will be relevant not only to CF testing but also to many other large-scale molecular genetic screening programs being considered in the future.