Harvard physician and researcher Christine E. Seidman developed a diagnostic test for hypertrophic cardiomyopathy (HCM), a genetic heart abnormality that is frequently the cause of sudden death in young athletes.

Already, the HCM test illustrates the promises and pitfalls of applied genetics. Among its promising points, the test can provide critical information. Families with an HCM history, for instance, often want to know whether a child carries a mutation linked to the condition. If so, parents may steer him or her toward sports and hobbies that are not overly strenuous. In addition, patients previously diagnosed with general cardiac hypertrophy can take the test to identify, or possibly downplay, HCM as the cause. Finally, patients with suspected HCM can learn which mutation they carry—useful knowledge, as several of the mutations can result in more severe forms of the condition.

However, like any other test for a complex genetic condition, the HCM test has gaps. "It's good at finding mutations in eight key genes, and that probably accounts for most cases of unexplained cardiac hypertrophy," says Allison Cirino, a genetic counselor at the Cardiovascular Genetics Center of Brigham and Women's Hospital. "But there are still other HCM genes out there, and a negative test result cannot rule them out."

Cost is another drawback. Because the comprehensive HCM test screens for more than 250 possible mutations across 14,188 base pairs of nucleotides, it is highly technical and thus expensive. Panel A alone costs $3,000 and Panel B costs $1,150. Alternatively, checking family members for a known mutation costs $250. Major insurance companies have covered the test for patients who received preapproval, Cirino notes.

The HCM test sequences DNA from a patient's blood sample, detecting mutations in the genes most commonly associated with HCM. The test is offered in two panels, HCM-A and HCM-B, for the following genes:

	HCM-A
	GENE	NAME
	MYH7	myosin, heavy chain 7
	MYBPC3	myosin-binding protein c, cardiac
	TNNT2	troponin t2, cardiac
	TNNI3	troponin i, cardiac
	TPM1	tropomyosin 1
	HCM-B
	GENE	NAME
	ACTC	actin, alpha, cardiac muscle
	MYL2	myosin regulatory light chain
	MYL3	myosin essential light chain, cardiac
	Source: www.hpcgg.org/lmm Photo: Asia Kepka

		There are two basic routes to the HCM test: The first, and most widely recommended, is through a cardiologist. The patient gives a blood sample at the doctor's office, which is then sent to the molecular medicine lab at Harvard Medical School—Partners Healthcare Center for Genetics and Genomics. About 6 weeks later, the cardiologist receives the results and reviews them with the patient. Alternatively, individuals can download test forms directly from the center's Web site (www.hpcgg.org), submit a 7-milliliter blood sample in a test tube by overnight mail, prepay for their test, and receive results in 6 weeks. Although formal genetic counseling is not part of the HCM test—it is available but not required—the center does have a staff counselor to answer specific questions by telephone. Meanwhile, independent genetic counselors work in all major urban areas nationwide (to find one, see the Web site of the National Society of Genetic Counselors www.nsgc.org). Many patients benefit from speaking with a qualified counselor, who can explain how a test works and what results mean, as well as answer questions.

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