ESCO2

The ESCO2 gene provides instructions for making a protein that is important for proper chromosome separation during cell division. Before cells divide, they must copy all of their chromosomes. The copied DNA from each chromosome is arranged into two identical structures, called sister chromatids. The ESCO2 protein plays an important role in establishing the glue that holds the sister chromatids together until the chromosomes are ready to separate.

Roberts syndrome - caused by mutations in the ESCO2 gene

At least 26 mutations have been found to cause Roberts syndrome. All of these mutations prevent the cell from producing any functional ESCO2 protein. Some mutations change single protein building blocks (amino acids), while others result in an abnormally short protein. The absence of functional ESCO2 protein causes some of the glue between sister chromatids to be missing around the chromosome's constriction point (centromere). In Roberts syndrome, cells respond to abnormal sister chromatid attachment by delaying cell division. Delayed cell division can be a signal that the cell should undergo self-destruction. The signs and symptoms of Roberts syndrome may be due to the loss of cells from various tissues during early development.

Researchers originally suspected that the varying severity of Roberts syndrome was caused by different types of mutations in the ESCO2 gene. They predicted that people with the mild form of the disorder would have mutations that reduced the activity of the ESCO2 protein, while those with the severe form would have mutations that completely eliminated the protein's function. However, all known mutations in the ESCO2 gene prevent the production of any functional ESCO2 protein. The underlying cause of the variation in disease severity remains unknown. Researchers suspect that other genetic and environmental factors may be involved.