Presenting diagnostic results from large-scale clinical mutation testing

With recent advances in genotyping methods, specifically improvements in DNA microarrays and chip-scanning instrumentation, it is now technically possible and economically feasible to test large numbers of patients for several thousand known mutations associated with Mendelian disease phenotypes. This possibility suggests numerous clinical applications of large-scale mutation arrays in molecular diagnosis and genetic risk assessment, such as prenatal testing for the most common mutations responsible for severe genetic disorders, screening for autosomal recessive or X-linked mutations, and predictive testing for a range of adult-onset disorders.

Several significant ethical issues must first be addressed if large-scale mutation testing is to be integrated effectively into clinical care. Large-scale mutation testing will generate an enormous amount of diagnostic information. Given the large number of mutations examined, it will not be possible to counsel patients on technical features of each individual component of a large-scale mutation array, such as false-positive and false-negative rates, as would be done in more traditional genetic testing procedures. Nor will it be possible to advise patients on specific medical interventions or confirmatory diagnostic tests associated with identifying each of several thousand possible mutations prior to testing, as frequently would be done in other situations in which genetic testing is recommended.

Since large-scale mutation testing will require a departure from these and other professional standards in clinical genetics, it is vitally important that this new form of genetic testing be introduced in a deliberative manner that is informed by the expectations, needs, and values of both patients and genetic professionals. This research study will examine patient and professional understandings of diagnostic results from large-scale clinical mutation testing. Its aims are to:

  1. Describe the attitudes and beliefs of patients and genetic professionals regarding the types of diagnostic possibilities that should be discussed with patients prior to large-scale clinical mutation testing
  2. Characterize the attitudes and beliefs of patients and genetic professionals regarding the types of diagnostic results that should be returned following large-scale clinical mutation testing 

These empirical results will be used to develop practical recommendations regarding the presentation of diagnostic results from large-scale clinical mutation testing. Systematic data on patients’s and professionals’s understandings of this new form of genetic testing are critically important, as these data will inform genetic-counseling practices, decisions about the return of diagnostic results and judgments about the appropriate use of large-scale mutation testing in patient care.