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Illustration: New England Journal of Medicine

There are several reasons why this is one of my favorite figures. First, it provides a visual representation of how seemingly unrelated loci can mutate to produce a common disease phenotype. Genetic mapping studies of hypertrophic cardiomyopathy demonstrated that a mutation located on any one of seven different chromosomes could cause the same clinical disease. The reason for this became quite clear when the actual disease genes were identified-each encodes a different component of the sarcomere, the contractile unite of heart cells. We then knew that hypertrophic cardiomyopathy is a disease of the sarcomere proteins.

This figure also explains why the clinical findings from some patients with hypertrophic cardiomyopathy are somewhat different. Although sarcomere gene mutations cause the disease, different protein defects can influence disease expression. Some cause late-onset hypertrophy; others cause early and severe disease. Presumable, this reflects the precise function of distinct sarcomere proteins. Finally, the interrelated components in this figure have always reminded me that human molecular genetic research is an interactive science requiring the collaboration of patients, families, physicians, and researchers alike.