SALL1

The SALL1 gene is part of a group of genes called the SALL family. These genes provide instructions for making proteins that are involved in the formation of tissues and organs during embryonic development. SALL proteins are transcription factors, which means they attach (bind) to specific regions of DNA and help control the activity of particular genes.

The exact function of the SALL1 protein is unclear. This protein is made in many tissues, including the kidneys, liver, and fetal and adult brain. Based on the effects of SALL1 mutations, researchers infer that this protein plays an important role in development of the hands (particularly the thumbs), ears, anus, kidneys, and other parts of the body before birth.

Townes-Brocks Syndrome - caused by mutations in the SALL1 gene

More than 55 mutations in the SALL1 gene have been identified in people with Townes-Brocks syndrome. Researchers originally believed that all of these mutations prevented one copy of the gene in each cell from making any protein, resulting in a shortage of SALL1 protein during development. More recently, they found that some mutations lead to the production of an abnormally small version of the SALL1 protein that malfunctions within cells. The malfunctioning protein interferes with normal copies of the SALL1 protein, preventing them from entering the nucleus to regulate gene activity. Scientists suspect that this type of genetic change likely underlies the more severe cases of Townes-Brocks syndrome. Mutations that reduce the amount of SALL1 protein are probably responsible for milder cases of this condition.

The SALL1 gene appears to be necessary for the normal development of many different organs and tissues before birth, which helps explain why mutations in this gene can cause the varied birth defects associated with Townes-Brocks syndrome. It is uncertain, however, how SALL1 mutations result in the specific features of this condition including an obstruction of the anal opening (imperforate anus), abnormally shaped ears, and hand malformations.