| Summary: | Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn Skoða/Opna(view/open) Hereditary central nervous system amyloid angiopathy occurring in Icelanders is the first human disease known to cause deposition of fragments of the alkaline microprotein cystatin C ( & -trace), forming amyloid fibrils in the walls of the brain arteries, leading to single or multiple strokes with fatal cerebral hemorrhages in most cases. Extensive pedigree studies based on ascertainment of 126 affected members in eight families who are originated in the same geographic area of Iceland, indicate that the autosomal dominant gene causing amyloid angiopathy has been transmitted over at least two centuries. Over 80% of those who have died from this disorder were less than 40 years. Carrier state is compatible with reaching old age. Of Icelanders, who died 1958-1968 from stroke at the age of 35 years or less, 18 individuals or 17% died from brain hemorrhage due to this amyloid angiopathy. The disorder is characterised by abnormally low value of cystatin C in the cerebrospinal fluid or one third of the average value found in comparable normal adults. This is the lowest value of cystatin C ever found in the CSF of man. In vivo diagnosis of this disease is now possible for the first time by simple estimation of cystatin C in the CSF, also in asymptomatic affected members. Recently only one amino acid difference (Glu for Leu) was found in the composition of a tryptic peptide corresponding to position 55-70 cystatin C (y-trace) numbering. It is conceivable therefore that a mutation has occurred leading to the production of an unusual cystatin C (y-trace) that is abnormally degraded, bound and/or precipitated. Restriction fragment length polymorphism analysis is under way to establish whether a defect in the cystatin C gene gauses the disease (28, 29). Cystatin C has recently been established as a major cysteine proteinase inhibitor by its strong homologies (up to 43%) with all sequenced human and animal ...
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