The STAG1gene provides instructions for making a protein that is part of a group of proteins called the cohesin complex. This complex helps keep the two copies of each chromosome together during cell division and also helps control how other genes are switched on and off during development.
In most people with a STAG1-related condition, there is a change (variant) in one copy of the STAG1gene that stops it working properly. This can happen because:
• A small piece of the gene is missing or extra
• The genetic code contains a “spelling mistake” that creates a stop signal too early
• The gene is cut or joined in the wrong way when making RNA (splicing)
These changes usually lead to too little STAG1 protein being made (this is called “haploinsufficiency”). Recent laboratory work has shown that some variants cause the faulty RNA to be broken down, so the cell makes much less STAG1 protein.
Having only one working copy of STAG1is enough for everyday survival, but it is not enough for typical brain and body development, which can lead to developmental delay, learning difficulties, and the other features described above. The change is present from conception and is not caused by anything the parents did or did not do.
Genetic testing (usually exome or genome sequencing) is needed to identify the STAG1 variant and confirm the diagnosis.
STAG1