Pitfalls in the interpretation of molecular diagnostic tests.

Abstract

Application of the tools of molecular genetics has vastly increased the power of genetic diagnosis, but also raises significant challenges in interpretation. Molecular tests can be used for diagnosis of an affected individual or determination of carrier status. Either direct mutation analysis or linkage analysis is used in various disorders. Major pitfalls in interpretation of direct tests include mistaking polymorphisms for mutations, inaccurate prognostication based on identification of a mutation, and misinterpretation of the implications of not finding a mutation. Interpretation of linkage tests must take account of the accuracy of proband diagnosis, interpretation of family relationships, and genetic recombination. Cognizance of these issues is vital to avoidance of clinical errors and must be incorporated into genetic counseling.