What are the genetic changes related to early-onset glaucoma ?
Approximately 10 percent to 33 percent of people with juvenile open-angle glaucoma have mutations in the MYOC gene. MYOC gene mutations have also been detected in some people with primary congenital glaucoma. The MYOC gene provides instructions for producing a protein called myocilin. Myocilin is found in certain structures of the eye, called the trabecular meshwork and the ciliary body, that regulate the intraocular pressure.  Researchers believe that myocilin functions together with other proteins as part of a protein complex. Mutations may alter the protein in such a way that the complex cannot be formed. Defective myocilin that is not incorporated into functional complexes may accumulate in the trabecular meshwork and ciliary body. The excess protein may prevent sufficient flow of fluid from the eye, resulting in increased intraocular pressure and causing the signs and symptoms of early-onset glaucoma.  Between 20 percent and 40 percent of people with primary congenital glaucoma have mutations in the CYP1B1 gene. CYP1B1 gene mutations have also been detected in some people with juvenile open-angle glaucoma. The CYP1B1 gene provides instructions for producing a form of the cytochrome P450 protein. Like myocilin, this protein is found in the trabecular meshwork, ciliary body, and other structures of the eye.  It is not well understood how defects in the CYP1B1 protein cause signs and symptoms of glaucoma. Recent studies suggest that the defects may interfere with the early development of the trabecular meshwork. In the clear covering of the eye (the cornea), the CYP1B1 protein may also be involved in a process that regulates the secretion of fluid inside the eye. If this fluid is produced in excess, the high intraocular pressure characteristic of glaucoma may develop.  The CYP1B1 protein may interact with myocilin. Individuals with mutations in both the MYOC and CYP1B1 genes may develop glaucoma at an earlier age and have more severe symptoms than do those with mutations in only one of the genes. Mutations in other genes may also be involved in early-onset glaucoma.