The EXOSC3gene gives instructions for making a protein that is part of a larger group of proteins called the exosome complex, which plays an important role in managing how genes are turned on and off. It does this by breaking down and processing RNA, which is like a message that tells cells what to do. When there are changes in EXOSC3, the exosome doesn't work properly especially in early-stage RNA molecules.
More serious forms of this condition have been linked to rare mutations, including small changes in the gene’s code (called missense and nonsense mutations) as well as missing or extra parts of the gene (deletions and duplications). People with these less common mutations often show more damage in the affected regions of the brain and usually have a much shorter life expectancy.
The most common pathogenic variant in the EXOSC3gene changes a single protein building block (amino acid). Specifically, it replaces aspartic acid with alanine at position 132 of the protein. This change is caused by a DNA mutation identified as c.395A>C (p.Asp132Ala). People who inherit two copies of this same alteration (one from each parent) often have a milder form of the condition than those who inherit two different mutations. However, a report described two siblings who had a milder case of the condition even though they had two different mutations in the EXOSC3gene: c.155delC and c.80T>G.
EXOSC3