A few different types of mutations to the HTRA1 gene have been observed in CARASIL patients. Nonsense mutations have been shown to cause no HTRA1 protein to be produced, while missense mutations have been shown to produce some HTRA1 protein, but with reduced activity. Regardless of whether or not HTRA1 protein is produced, or its activity is greatly reduced, the normal regulatory activity of the HTRA1 protein is lost. This means that TGF-β (transforming growth factor beta) signaling cannot be repressed as normal. When TGF-β activity goes unchecked, it alters the structure of the small blood vessels in the brain, increasing an individuals risk of stroke and other neurological abnormalities. Abnormally increased TGF-β activity is also suspected to be involved in the alopecia and lumbago seen in CARASIL patients, but that has not been confirmed and the mechanism is not yet known. CARASIL is a disease characterized by damage to the small blood vessels of the brain. When blood vessels in the brain are damaged, blood flow can be reduced or stopped leading to stroke. It can also lead to a variety of different symptoms depending on what area of the brain has lost its blood supply. This is what causes the spasticity in the limbs, slurred speech, urinary incontinence, and dysarthria seen in some patients. Progressive damage to and loss of the white matter, or myelinated areas, in the brain leads to some of the other neurological symptoms, such as forgetfulness progressing to dementia, mood changes, confusion, and apathy.
Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy
Hereditary cystatin C amyloid angiopathy
Walker–Warburg syndrome
Hereditary diffuse leukoencephalopathy with spheroids
Cerebral amyloid angiopathy
Familial British dementia
Moyamoya disease
Subacute sclerosing panencephalitis