The Case of “Missing Causal Genes” and the Practice of Medicine
A Sherlock Holmes Approach of Deductive Reasoning
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The practice of medicine is an exceedingly gratifying privilege, a notion that is commonly shared among the physicians. Also commonly understood but often not expressed is the humbling nature of this practice. Seldom, if ever, we know the true answers to our patients’ questions. Yet, we adeptly offer explanations, commonly based on the group data, and yet the essence of the practice of medicine is recognizing the uniqueness of the individual and his/her disease. To quote Sir William Osler, the father of western medicine, “the good physician treats the disease; the great physician treats the patient who has the disease.” Still, our answers typically gratify the patients and perhaps give the physicians an incontrovertibly false sense of being omniscient.
The landscape of the practice of medicine has been recently enriched with the entry of the medical genetics. The impetus provided by the recent elucidation of the genetic causes of single-gene cardiovascular diseases has ushered in clinical applications of the molecular genetic discoveries and along with it our exuberance about genetic-based diagnosis, risk stratification, prevention, and treatment. Molecular Genetic testing is now routinely performed as part of the medical evaluation of patients with medical conditions commonly recognized as single-gene diseases, such as inherited cardiomyopathies and arrhythmic syndromes.1–3 It is also being advocated for risk stratification of patients with complex phenotypes, albeit its validity remains unsettled. Along with these advances, the need to educate and train the practicing physicians in understanding the fundamentals of genetics and their applications to the practice of medicine are increasingly recognized.4
Despite the remarkable progress in elucidation of genetic causes of cardiovascular diseases during the past 25 years, the causal genes in ≈30% to 50% of various single-gene cardiovascular diseases, including hereditary cardiomyopathies and arrhythmic syndromes, have yet-to-be identified (Figure). The common causal …