Knowledge about molecular pathology of hereditary cystatin C amyloid angiopathy (HCCAA), also called hereditary cerebral hemorrhage with amyloidosis, Icelandic type, has increased greatly in the last decade. The disorder has an autosomal dominant mode of inheritance and causes fatal brain hemorrhage in normotensive young adults. It is due to a mutation in the gene encoding the cysteine proteinase inhibitor, cystatin C. A single nucleotide is substituted, A for T, in the codon 68, resulting in glutamine replacing leucine in the protein sequence. This variant protein has an increased tendency to aggregate and forms heavy depositions of amyloid in the walls of the small arteries and arterioles of the brain. The amyloid deposition leads to arterial damage with single or multiple strokes. In the following review the clinical features, family studies, pathology, biochemistry and molecular genetics of HCCAA are addressed.
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