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Tailing the cause of a rare heart disease

Using genetic analyses and the translucent tail of a fish, researchers have pinpointed the underlying cause of a rare, mysterious heart disease that is preceded by hearing loss. Discovering the genetic cause of this disease provides researchers with a wealth of new ideas about the molecules involved in building the developing heart, as well as how diseases weaken heart muscle.

In an advance online publication on February 27, 2005, in the journal Nature Genetics, Howard Hughes Medical Institute investigators Christine E. Seidman and Jonathan G. Seidman and their colleagues identified the mutation that causes the disorder, dilated cardiomyopathy preceded by sensorineural hearing loss. The Seidmans and their colleagues at Harvard Medical School collaborated with researchers at University Hospital Wrzberg in Germany, Massachusetts General Hospital, Children's Hospital Boston and The Wellcome Trust Sanger Institute in Britain.

In dilated cardiomyopathy, muscle weakness causes the left ventricle to stretch. As a result, the heart becomes enlarged to the point where it can no longer pump blood efficiently. In earlier studies of patients with cardiomyopathy preceded by hearing loss, the Seidmans and their colleagues identified a region of chromosome 6 as the location of the culprit gene.

In the latest study, they sought to pinpoint the gene and identify the mutation that was responsible. A search of the human genome database identified candidate genes in the region, and subsequent tissue analysis revealed that one gene, called EYA4, was expressed in both the heart and the cochlea of the ear. The researchers confirmed that affected people possess a characteristic mutation of the EYA4 gene, a finding which offered surprises, said Christine Seidman.

"The EYA4 gene had been implicated in hearing loss before, but in none of the patients where mutations had been characterized had there ever been an abnormality of the heart reported," she said. The
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
27-Feb-2005


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