In 1993, shortly after Borsari graduated from college, her doctor heard an irregular heartbeat during a routine exam.

This time, an echocardiogram confirmed Borsari's fears: hypertrophic cardiomyopathy (HCM). A genetic abnormality that enlarges muscle cells in the heart's left ventricle, HCM can cause a sometimes-fatal irregular heartbeat, heart failure, exercise intolerance, and chest pain. With an HCM diagnosis in hand, Borsari began to actively manage her health, with frequent medical checkups and more careful health-related decisions. Today, as a 39-year-old mother of two, she leads a pleasantly ordinary life in the Boston suburbs.

HCM is the primary cause of sudden death in people under 30. Young athletes in particular, researchers say, suffer sudden cardiac death at two to three times the rate of others of their generation. Although estimates vary, as many as 300 young athletes may die from sudden cardiac death every year in the United States alone—collapsing at soccer games or swim meets, for example, or simply during practice. One of Borsari's uncles died as a teenager, heading to the football field, roughly 50 years ago. (The other two died at ages 26 and 33.)

If HCM is detected in time, doctors can manage the condition with surveillance, lifestyle changes, and, sometimes, an implantable defibrillator. But young adults are not universally screened for heart conditions, and early HCM symptoms—such as shortness of breath—may easily be mistaken for more common conditions such as asthma. Although a family history of HCM suggests the need to test children, many—like Borsari—develop clinical symptoms later. For patients and families, dealing with this uncertainty is costly, emotionally draining, and fraught with physical danger.

For patients and families, dealing with this uncertainty is costly, emotionally draining, and fraught with physical danger.

Now, a new genetic test may allow early identification and diagnosis of those at greatest risk for developing HCM. The test can confirm an HCM diagnosis in patients who show clinical symptoms of the disease and can provide further information for individuals at risk for the condition. Administered by the Harvard Medical School—Partners Healthcare Center for Genetics and Genomics, the test detects mutations in eight genes that account for up to 70 percent of HCM in patients with clinical symptoms.

HHMI investigator Christine E. Seidman and her husband, HHMI alumni investigator Jonathan G. Seidman, both of Harvard Medical School, developed the HCM test. The Seidmans have spent the past two decades identifying and explaining the molecular mechanics behind HCM. They tracked its incidence through families, analyzed the genomes of affected family members, mapped relevant disease genes, and, ultimately, pinpointed many of the telltale mutations that cause the condition. The couple currently is working to understand how these mutations trigger signaling molecules that cause heart muscle cells to grow abnormally.

Cardiovascular geneticist Jonathan Seidman brings a long-standing interest in the molecular causes of hypertrophy to the hunt for HCM genes. In particular, he has analyzed the mutations linked to the disease and currently heads efforts to determine how HCM genes may contribute to the risk of hypertrophy in other cardiac conditions.

Meanwhile, Christine Seidman sees HCM from the perspective of both researcher and physician. As director of the Cardiovascular Genetics Service at Brigham and Women's Hospital, she sees patients several days each month. Most days of any given week, however, she can be found at the lab bench. Her research efforts on HCM and other cardiac conditions, such as dilated cardiomyopathy, were recently recognized with her election to the National Academy of Sciences.

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