This is the first in an occasional series in which we will discuss genes of interest on chromosome 18. These are the genes that we believe are responsible for specific features of one of the chromosome 18 conditions.

One goal of the Chromosome 18 Clinical Research Center is to understand how a chromosome deletion or duplication can lead to medical and developmental issues. In order to do this, we must learn what the various genes on chromosome 18 do. We must also learn what happens when one copy of the gene is deleted. We believe that, in nearly all case, the amount of product made by one gene is enough for the cells of the body to function. However, there are a handful of genes that require the presence of two copies in order to do their job. If there is an extra or missing copy of these genes, they cannot do their job properly. These are the genes responsible for the features associated with chromosome 18 conditions. SETBP1 is one of these genes.

SETBP1 stands for "SET binding protein 1". Scientists are still working to understand its role in the body. We know that it is involved in DNA replication. In addition, evidence suggests that the protein encoded by this gene is found in a wide range of tissues, including the brain. This suggests that changes involving this gene may impact the development and/or function of neural cells.

SETBP1  is located within band 18q12.3. Individuals with Proximal 18q- may be missing this gene. In our population of 12 people with Proximal 18q-, 8 are missing this gene. Individuals that have Distal 18q- are not missing this gene.

Proximal 18q- may cause some degree of cognitive disability, often in the mild range. Children with this condition typically do not have major birth defects or facial differences. One of the most characteristic features of proximal 18q- is an expressive speech delay. This means that they understand more than they are able to speak. We believe that the SETBP1 gene is responsible for this expressive speech delay. This is because we and others have identified people with a deletion of only this gene that have expressive speech delay.  

It is interesting to note that a different kind of genetic change, called a missense mutation, in  SETBP1 may lead to a completely different picture. This is because a missense mutation causes a changed gene product that actually interferes with the functional copy of the gene . This is different from people who are missing a copy of the SETBP1 gene altogether and consequently have a reduced amount of the protein product. People who have a missense mutation may have a condition called Schinzel-Gideon syndrome. This is characterized by severe cognitive disability, multiple birth defects, and a significantly shortened lifespan. This is in sharp contrast to people that have a complete deletion of SETBP1. This illustrates why, when you hear that a certain gene on chromosome 18 is associated with a syndrome or disease, it may have no implications for people with a deletion or duplication on chromosome 18.

In summary, SETBP1 is one of the handful of genes that have been directly linked with specific features of the chromosome 18 conditions. As time goes on, we look forward to finding more links between individual genes and outcomes.