Question: What are the genetic changes related to Opitz G/BBB syndrome ?
Answer: X-linked Opitz G/BBB syndrome is caused by mutations in the MID1 gene. The MID1 gene provides instructions for making a protein called midline-1. This protein attaches (binds) to microtubules, which are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). Microtubules help cells maintain their shape, assist in the process of cell division, and are essential for the movement of cells (cell migration). Midline-1 assists in recycling certain proteins that need to be reused instead of broken down. MID1 gene mutations lead to a decrease in midline-1 function, which prevents protein recycling. The resulting accumulation of proteins impairs microtubule function, leading to problems with cell division and migration. It is unclear how these changes disrupt normal development and cause the signs and symptoms of Opitz G/BBB syndrome. Autosomal dominant Opitz G/BBB syndrome is caused by changes in chromosome 22. Some affected individuals have a deletion of a small piece of chromosome 22, specifically at an area of the chromosome designated 22q11.2. Because this same region is deleted in another condition called 22q11.2 deletion syndrome, researchers often consider Opitz/GBBB syndrome caused by this genetic change to be a form of 22q11.2 deletion syndrome. It is not known which of the deleted genes contribute to the signs and symptoms of Opitz G/BBB syndrome. In other people, autosomal dominant Opitz/GBBB syndrome is caused by a mutation in the SPECC1L gene, which is near the 22q11.2 region but is not in the area that is typically deleted in other individuals with autosomal dominant Opitz G/BBB syndrome or 22q11.2 deletion syndrome. The SPECC1L gene provides instructions for making a protein called cytospin-A. This protein interacts with components of the cytoskeleton and stabilizes microtubules, which is necessary for these fibers to regulate various cell processes including the movement of cells to their proper location (cell migration). Cytospin-A is particularly involved in the migration of cells that will form the facial features. Mutations in the SPECC1L gene result in the production of a protein with a decreased ability to interact with components of the cytoskeleton. As a result, microtubules are disorganized and cells have trouble migrating to their proper location. Because the SPECC1L gene plays a role in facial development, mutations in this gene likely account for the cleft lip and palate seen in some individuals with Opitz G/BBB syndrome, but it is unclear how SPECC1L gene mutations cause the other features of this disorder. Some people with Opitz G/BBB syndrome do not have any of the genetic changes described above. The cause of the condition in these individuals is unknown.
Source: GHR