Molecular Diagnosis and Genetic Testing

Abstract

The capability to assay for the status of individual genes or proteins in patient blood or tissues has grown exponentially over the last two decades. Molecular diagnostics has had a particularly important impact on the practice of neurology, both due to the keen interest of the practicing neurologist and the fact that many of the first identified disease genes have been for inherited neurological conditions. With the dramatically expanding knowledge of the primary biochemical defect for hundreds of disorders comes the anticipation that pathophysiological cascades can be slowed or halted, or primary biochemical deficiencies replaced. While this hope has yet to be realized, molecular human genetics has transformed the way in which the inherited and noninherited neurological diseases are researched, and experimental therapeutics are pursued. Finally, molecular diagnostics can provide a definitive diagnosis to a patient (both symptomatic and presymptomatic) while also permitting the genetic counseling of the patient’s family.

With the increased knowledge of the underlying genetic abnormality in a patient come ethical and legal hazards which are increasingly recognized by patients, health-care professionals, employers, and legislative oversight committees. These hazards are complicated by the fact that few, if any, molecular diagnostic tests have been approved by the Food and Drug Administration (FDA). The reluctance of most laboratory medicine divisions to provide large-scale molecular diagnostics services is a product of the advanced molecular expertise required for many assays, expensive and nonautomated equipment, and the relatively poor reimbursement from third-party payers. This same testing milieu results in a dispersion of specific genetic tests among hundreds of highly specialized laboratories, and navigating the maze of possible referral sites for each specific gene or protein test is often a daunting task. Fortunately, many Web-based resources are available that make finding an appropriate molecular testing laboratory relatively simple. Getting these tests paid for by Medicare, Medicaid, and private insurance remains more challenging, and this in turn may affect equal access to care.