CCM2

Cerebral cavernous malformation

Dozens of mutations in the CCM2 gene have been identified in families with cerebral cavernous malformations, which are collections of blood vessels in the brain that are weak and prone to leakage. Most of these mutations result in an abnormally short or malformed malcavernin protein that does not function. A shortage of this protein likely impairs the function of the complex. As a result, RhoA-GTPase signaling is turned on abnormally, weakening cellular junctions and increasing the permeability of blood vessel walls. The increased leakage into the brain can cause health problems such as headaches, seizures, and bleeding in the brain (cerebral hemorrhage) in some people with cerebral cavernous malformations.

Mutations in the CCM2 gene are involved in approximately 15 percent of all familial cerebral cavernous malformation cases.