What are the genetic changes related to hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome ?
Mutations in the COL4A1 gene cause HANAC syndrome. The COL4A1 gene provides instructions for making one component of a protein called type IV collagen. Type IV collagen molecules attach to each other to form complex protein networks. These protein networks are the main component of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. Type IV collagen networks play an important role in the basement membranes in virtually all tissues throughout the body, particularly the basement membranes surrounding the body's blood vessels (vasculature).  The COL4A1 gene mutations that cause HANAC syndrome result in the production of a protein that disrupts the structure of type IV collagen. As a result, type IV collagen molecules cannot attach to each other to form the protein networks in basement membranes. Basement membranes without these networks are unstable, leading to weakening of the tissues that they surround. In people with HANAC syndrome, the vasculature and other tissues within the kidneys, brain, muscles, eyes, and throughout the body weaken.