The GUSB gene contains the instructions for making an enzyme called beta-glucuronidase. This enzyme plays an important role in breaking down certain complex sugars known as glycosaminoglycans (GAGs), which the body naturally produces and recycles.
In Mucopolysaccharidosis type VII (MPS7, also called Sly syndrome), both copies of the GUSB gene have changes (called mutations) that prevent the body from making enough working enzyme. When this happens, the sugars that are normally broken down build up inside the cells, especially in parts of the body like the bones, liver, spleen, and brain. Over time, this buildup causes damage and leads to the symptoms of the disease.
There are many different types of mutations that can affect the GUSB gene:
• Missense mutations: These are small changes in the gene that cause the enzyme to be made with the wrong building block (like a typo in a recipe). The enzyme may still be made, but it doesn’t work properly.
• Nonsense mutations: These changes cause the body to stop making the enzyme too early, so it ends up incomplete and cannot do its job.
• Deletions: Sometimes small parts of the gene are missing, which can lead to a faulty or missing enzyme.
• Splice site mutations: These affect how the genetic message is read and can also result in an enzyme that doesn’t work.
Deletions and duplications in the GUSB gene have been reported only in isolated cases and do not represent a common disease mechanism.
GUSB