Identifying sarcomere gene mutations in hypertrophic cardiomyopathy: a personal history

CE Seidman, JG Seidman - Circulation research, 2011 - Am Heart Assoc
CE Seidman, JG Seidman
Circulation research, 2011Am Heart Assoc
This review provides an historical and personal perspective on the discovery of genetic
causes for hypertrophic cardiomyopathy (HCM). Extraordinary insights by physicians who
initially detailed remarkable and varied manifestations of the disorder, collaboration among
multidisciplinary teams with skills in clinical diagnostics and molecular genetics, and hard
work by scores of trainees solved the etiologic riddle of HCM and unexpectedly
demonstrated mutations in sarcomere protein genes as the cause of disease. In addition to …
This review provides an historical and personal perspective on the discovery of genetic causes for hypertrophic cardiomyopathy (HCM). Extraordinary insights by physicians who initially detailed remarkable and varied manifestations of the disorder, collaboration among multidisciplinary teams with skills in clinical diagnostics and molecular genetics, and hard work by scores of trainees solved the etiologic riddle of HCM and unexpectedly demonstrated mutations in sarcomere protein genes as the cause of disease. In addition to celebrating 20 years of genetic research in HCM, this article serves as an introductory overview to a thematic review series that will present contemporary advances in the field of hypertrophic heart disease. Through the continued application of advances in genetic methodologies, combined with biochemical and biophysical analyses of the consequences of human mutations, fundamental knowledge about HCM and sarcomere biology has emerged. Expanding research to elucidate the mechanisms by which subtle genetic variation in contractile proteins remodel the human heart remains an exciting opportunity, one with considerable promise to provide new strategies to limit or even prevent HCM pathogenesis.
Am Heart Assoc