18q- Genes Under Investigation
We have talked about genes that we know to be linked to features of 18q-. However, there are many more genes that we are still working to understand. The genes discussed below are known as candidate genes. These are genes that we believe may play a role in the features of 18p-, but additional evidence and research will be necessary to confirm that suspicion.
TXNL1 (54,270,053-54,306,270). There has been a suggestion that deletions of this gene can lead to an increased risk of autism and/or learning disabilities. In addition, a small number of individuals with deletions of this gene have had other features, such as birth defects and seizures. However, we are still working to understand whether it is this gene that is responsible for the findings. More work remains to be done to truly understand what a TXNL1 deletion actually means.
NETO1 (70,409,549-70,534,810). Mice that are missing this gene seem to have difficulty with certain cognitive functions. For example, they have difficulties learning to adapt to changes in their environment. They have trouble with remembering information about their environment and where they are within that environment. However, deletions of this gene have also been found in people that have no medical or developmental concerns. So, we still have much to learn about this gene, and what it means for people with 18q-.
CYB5A (71,920,527-71,959,251). People who have a mutation in both copies of this gene develop a specific condition called 17,20 lyase deficiency, which leads to changes in the development of male genitalia. We do not know whether or not one missing copy of the gene, as is the case in some individuals with distal 18q-, is enough to cause genital anomalies. We know that males with 18q- frequently have genital changes, such as cryptorchidism, hypospadias, and micropenis. In addition, no male that has a deletion of this genes has fathered children. However, most males with a deletion of this gene have not undergone a fertility evaluation. Additional research will be required to determine what role, if any, CYB5A plays in male fertility.
MBP (74690789-74844774). There had been a great deal of interest in this gene because it is a candidate gene for dysmyelination, a well-known feature of distal 18q-. In addition, deletions of MBP may be linked with the type of sensorineural hearing loss frequently seen in individuals with distal 18q-. We are still working to understand what role, if any, this gene plays in the features of distal 18q-.
NFATC1 (77,160,326-77,289,323). Mice who are missing this particular gene seem to have some immune changes. We know that people with 18q- have a higher incidence of autoimmune conditions, so this is a particularly interesting finding. However, there is also some evidence that missing one of these genes might protect someone from autoimmune conditions. Therefore, the relationship between this gene and immune function is unclear. In addition, there are some reports that people who are missing this gene may be at a higher risk for degenerative lumbar scoliosis. Indeed, people with distal 18q- are at an increased risk for scoliosis. Again, additional research is necessary to determine the role that NFATC1 plays in distal 18q-.