Gene specific therapy for cardiac disease: the case of long QT syndrome.
Molecular genetics is progressively entering clinical practice. This new approach is modifying medical thinking as it becomes possible to diagnose diseases in their presymptomatic phase. It is therefore important for physicians to become acquainted with the "language" and the "methodology" of molecular biologists in order to balance opposite attitudes of the novice, i.e. skepticism and over-expectation, and to establish a fruitful interaction with the molecular diagnostic laboratories. Long QT syndrome is an inherited disease that few years ago was still called "idiopathic" as the underlying causes were unknown. Clinicians are now becoming aware that what was considered as one disease is actually the common phenotype of defects in at least five different LQT-related genes and that therefore clinical heterogeneity is likely to parallel genetic heterogeneity. The first steps have been undertaken to define the relative prevalence of the molecular variants of LQTS, to develop gene-specific therapy and to perform risk stratification based on the molecular defect. In this article, current knowledge of the molecular bases of LQTS is reviewed and criteria are proposed to help defining 1) when it is appropriate to attempt molecular diagnosis, 2) how to interpret results of the diagnostic laboratory and 3) how molecular diagnosis may affect patients management.
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S G
SG
Molecular Cardiology Laboratories, Fondazione Salvatore Mangeri, Pavia, Italy. silvia.priori@netitalia.it
D005817:Genetic Counseling; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008133:Long QT Syndrome / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D017354:Point Mutation