Researchers identify gene causing fatal heart condition

A fatal heart condition found in Bedouin Arab children led researchers to discover genes that may be causing an array of heart problems.A team of researchers from the Weizmann Institute of Science in Rehovot, Israel, and the Sheba Medical Center …

A fatal heart condition found in Bedouin Arab children led researchers to discover genes that may be causing an array of heart problems.A team of researchers from the Weizmann Institute of Science in Rehovot, Israel, and the Sheba Medical Center in Tal Hashomer has identified a gene causing polymorphic ventricular tachycardia (PVT), a fatal heart condition. Characterized by a fast and irregular heartbeat, seizures, and in certain cases, sudden death, PVT primarily affects young children.

The mutation, which was found in a Bedouin tribe in Northern Israel, had previously caused the death of nine children in this tribe, in some cases from the same family.

“The new finding is expected to improve the screening for and treatment of this fatal disease, as well as opening a window to a better understanding of other heart conditions,” said Dr. Nili Avidan of the Weizmann Institute’s Department of Molecular Genetics. “We believe that mutations in this and other biochemically related genes may lie behind a number of as yet largely unsolved heart disorders.”

The team found that the disease is caused by a mutation in the gene known as Calsequestrin 2, which plays a vital role in the contraction and relaxation of the heart. The mutation impairs the ability of the CASQ2 protein to attract and release calcium ions upon demand.

The study was performed by doctoral student Hadas Lahat of the Danek Gartner Institute of Human Health Genetics in Israel, and her advisors and was published in the Journal of Human Genetics.

The study began when an eight-year-old girl in the tribe fainted following exercise, and was admitted to the Rambam Medical Center in Haifa. Her two younger brothers suffered from the same symptoms, and two other siblings had previously died of the disease.

While doctors believed that the children’s symptoms were due to tachycardia, they were unable to identify the precise cause. The family then turned to Prof. Michael Eldar, chief of the heart institute at the Sheba Medical Center who diagnosed the children as suffering from PVT. During his meeting with them, Eldar learned that several other families in the village had a similar medical history.

The girl’s family belongs to a Bedouin community in northern Israel, thought to be the descendants of three brothers who had settled there more than 200 years ago. The nature of the disease and the common Bedouin custom of familial intermarriage alerted researchers to possible genetic involvement.

Hypothesizing that one of these brothers had harbored a genetic mutation, Lahat visited the community and tested the families. It appeared she was on the right track. In seven families alone, thirteen children were identified as having PVT and were given appropriate medication. Nine untreated children in these families had earlier died from this condition.

The researchers had yet to identify the exact gene responsible for PVT from a possible 80 candidate genes, but information was available for only half of the 80 suspect genes. Lahat and her supervisor, Dr. Elon Pras, decided to approach Weizmann Institute scientists for help.

Scientists at Weizmann initially had little success, yet as the Human Genome Project that maps the human gene pool generated new information at an increasing speed, the researchers came upon the newly mapped gene, Calsequestrin 2. The CASQ2 protein appeared as a good candidate because it serves as a calcium ion reservoir in heart muscle cells. By binding, holding, and releasing calcium ions, the CASQ2 protein could thus play a key role in the contraction and relaxation of heart muscles.

The researchers soon found that the children suffering from PVT had a mutation in their CASQ2 gene, and were able to pinpoint how things had earlier gone wrong in those who had died.