Carasil and htra1: an early adulthood syndrome

Abstract

Cerebral Autosomal Recessive Arteriopathy Subcortical Infracts Leukoencephalopathy (CARASIL), is an autosomal recessive disorder inherited by two copies of an abnormal gene from some trait, one from each parent. Person with this disorder may have a change in deep white matter in brain; and this disorder can be characterized by damage to small blood vessels in brain. Increasing muscle tone, slurred speech, stiff movement of legs, gait disturbance, spondylosis, sparse hair are the major symptoms. But the ultimate cause of this disorder can lead to loss of memory, cognitive impairment. This disorder can be caused in early adulthood i.e., between 20-40 years of age. CARASIL has first reported in Japan, later occurred in China and Caucasian population. A neurological disorder named Binswanger’s disease (BD) and chronic immunological disorder multiple sclerosis are main different alternation of this disease. Mutation requires the high temperature resultant, A serine peptidase 1 causes CARASIL, so it is a serine protease.

Serine protease HTRA1 is an enzyme that in humans is encoded by HTRA1 gene. HTRA1 protein is composed of four distinct protein domains. This is located on the long (q) arm of chromosome 10 in a region known as 10q26. This protein is a secreted enzyme that is proposed to regulate the availability of insulin like growth factors (IGF) by cleaving IGF binding proteins. HTRA1 enzyme helps breakdown many other kinds of proteins in this space surrounding cells (extracellular matrix). This is attached to protein in Transforming Growth Factor Beta (TGF-beta) and slows down their ability to send chemical signals. Variant known as rs11200638 is found in an area of gene called promoter region which starts the production HTRA1 enzyme. It is unclear how of polymorphism in the HTRA1 gene might be an age-related macular degeneration.

So at last, we can conclude that CARASIL is related to brain inherited from the abnormal genes caused to small arteries and to the specific area of deep brain in higher function; tissue loss due to lack of oxygen where small arteries get blocked destruction to myelin an oily substance covers and protects the nerve fibers in CNS.