Genomics research: New genetic 'hit list' may underlie susceptibility to sudden cardiac death

ehensive analysis of a large group of healthy persons for gene mutations that could increase susceptibility to sudden cardiac death.

Surprising Prevalence of Variants

Inherited long QT syndrome occurs when a defect develops in one or more of the genes that program the ion channels of the heart. The ion channels are "electrical tunnels" that produce and control the heart's electrical activity. A key finding of this study: far more potassium channel variants exist than were anticipated. The study identified 49 distinct variants among the healthy population examined -- 36 of the variants or 73 percent were previously unknown. Eighty-six percent of the variants were found only in specific ethnic groups. When researchers excluded the most common and established potassium channel variants, one in three blacks and one in seven whites studied were found to harbor at least one variant. Based on previous studies, a potassium channel mutation causing inherited long QT syndrome should be expected in only one out of every 10,000 individuals.

Impacts Future Diagnosis for Blacks

The researchers say the findings have a profound impact on diagnosis and future testing for long QT syndrome. Because of the large number of variants found in such a diverse, healthy group of individuals, researchers say physicians need to use extreme care in diagnosing newly-discovered variants as disease-causing mutations -- especially among minority patients.

"This new compendium of channel variants is a 'hit list' of suspects for investigators aiming at the larger issue of sudden cardiac death," says Dr. Ackerman. "We don't know if any of these variants cause increased susceptibility to external causes, such as medications, but the new data provides an exciting opportunity for important studies."

For example, one variant -- Q9E-MiRP1 -- previously identified as a disease-causing arrhythmia mutation -- had not been seen in over one thousand cont

Contact: Bob Nellis
Mayo Clinic

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