Scientists Identify Gene Linked to Fatal Heart Condition

This is a fatal heart condition, primarily affecting young children, that is characterized by a fast and irregular heartbeat, seizures, and in certain cases, sudden death.

As reported in the December 2001 issue of the American Journal of Human Genetics, researchers found that the disease is caused by a mutation in the gene known as Calsequestrin 2 (CASQ2), 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 current study focused on a Bedouin tribe in Northern Israel, where PVT had caused the death of nine children, in some cases from the same family. Initially, the researchers were faced with trying to identify the exact gene responsible for PVT from a possible 80 candidate genes. Fortunately, as the work progressed, information from the Human Genome Project became available. The newly mapped gene for CASQ2 emerged as a good prospect because this protein serves as a calcium ion reservoir in heart muscle cells. Indeed, only four months earlier a different research team had found that a mutation in the gene RYR2, which belongs to the same cellular pathway as CASQ2, also causes a form of PVT.

The researchers were able to confirm that the Bedouin children suffering from PVT had a mutation in their CASQ2 gene. While the mutation was caused by only a single base change, from G to C, in one of the DNA's nucleotides, this change caused the body to produce the positively charged amino acid histidine instead of negatively charged aspartic acid, which impairs the CASQ2 protein's ability to attract and release calcium ions, leading to heart failure.

"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,” says 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.”




Related Links:
Weizmann Institute of Science
Sheba Medical Center