ZSWIM6-related intellectual disability is due to a very small ‘spelling mistake’ in one copy of the ZSWIM6 gene.
It is called an ‘autosomal dominant’ mutation. This means that it affects an autosomal gene which is a gene located on a numbered chromosome (in this case chromosome number 5) and the condition affects males and females in the same way. Dominant means that the gene change occurs in only one of the pair of genes to cause the health condition.
Individuals with ZSWIM6-related intellectual disability typically come from families that have no family history of intellectual disability. The ZSWIM6 gene change occurs for the first time in the person with the disorder and is not carried by either parent. This is called a ‘de novo’ gene change.
On occasion, one parent may have the ZSWIM6 mutation (gene change) in some of their egg or sperm cells but not be affected, as no other organ in their body has the mutation. This is called germline mosaicism and means that there is a very small chance that they may have another affected child. It would be important for parents of an individual with ZSWIM6-related intellectual disability to discuss this possibility with their genetics team if they were planning another pregnancy, so that they can obtain accurate genetic counseling.
While it is unlikely that an individual with a ZSWIM6-related disorder with severe or profound intellectual disability will partner and have children, a carrier of a ZSWIM6 mutation that does go on to have children will have a 50% chance with each pregnancy of passing on the ZSWIM6 mutation. Children who inherit a ZSWIM6 mutation from their parent will experience a similar level of challenges as their parent and some may even experience difficulties and symptoms not seen in their parent. Genetic counselling is available through the local genetic service when planning a pregnancy and in early pregnancy.
For ZSWIM6-related intellectual disability the specific gene change is called p.Arg913Ter. This is called a ‘stop’ variant. It means that an early ‘stop’ message is put into the gene code (at amino acid number 913), resulting in this copy of the ZSWIM6 gene making a much shorter version of the ZSWIM6 protein. This shorter copy of the protein cannot do its job properly in the cells of the body. We think this genetic change in particular results in differences in how ZSWIM6 regulates the development and function of nerve cells in the body. More research is needed to fully understand the effect of this gene change at the level of individual cells.