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 that had died. They discovered that the mutation was surprisingly small { characterized by only a single base change, from G to C, in one of the DNA's nucleotides. Nevertheless this change causes the body to produce the amino acid histidine instead of aspartic acid, which impairs the CASQ2 protein's ability to attract and release calcium ions. The protein carries a very strong negative charge, thus binding a large number of positively charged calcium ions and releasing them when necessary, says Avidan. Unfortunately, in the mutated CASQ2 protein, the overall negative charge is smaller, since the single base change replaces the aspartic acid which is negatively charged { with the positively charged histidine. This most likely damages the protein's ability to attract calcium ions, leading to heart failure.

'"/>

Contact: Jeffrey Sussman
jeffrey@acwis.org
212-895-7951
American Committee for the Weizmann Institute of Science
4-Mar-2002