[CYTC_HUMAN] Defects in CST3 are the cause of amyloidosis type 6 (AMYL6) [MIM:105150]; also known as hereditary cerebral hemorrhage with amyloidosis (HCHWA), cerebral amyloid angiopathy (CAA) or cerebroarterial amyloidosis Icelandic type. AMYL6 is a hereditary generalized amyloidosis due to cystatin C amyloid deposition. Cystatin C amyloid accumulates in the walls of arteries, arterioles, and sometimes capillaries and veins of the brain, and in various organs including lymphoid tissue, spleen, salivary glands, and seminal vesicles. Amyloid deposition in the cerebral vessels results in cerebral amyloid angiopathy, cerebral hemorrhage and premature stroke. Cystatin C levels in the cerebrospinal fluid are abnormally low. Genetic variations in CST3 are associated with age-related macular degeneration type 11 (ARMD11) [MIM:611953]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.
[CYTC_HUMAN] As an inhibitor of cysteine proteinases, this protein is thought to serve an important physiological role as a local regulator of this enzyme activity.
↑ Levy E, Lopez-Otin C, Ghiso J, Geltner D, Frangione B. Stroke in Icelandic patients with hereditary amyloid angiopathy is related to a mutation in the cystatin C gene, an inhibitor of cysteine proteases. J Exp Med. 1989 May 1;169(5):1771-8. PMID:2541223
↑ Abrahamson M, Jonsdottir S, Olafsson I, Jensson O, Grubb A. Hereditary cystatin C amyloid angiopathy: identification of the disease-causing mutation and specific diagnosis by polymerase chain reaction based analysis. Hum Genet. 1992 Jun;89(4):377-80. PMID:1352269
↑ Zurdel J, Finckh U, Menzer G, Nitsch RM, Richard G. CST3 genotype associated with exudative age related macular degeneration. Br J Ophthalmol. 2002 Feb;86(2):214-9. PMID:11815350