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- Jensson, O, et al.
(författare)
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Hereditary cystatin C (gamma-trace) amyloid angiopathy of the CNS causing cerebral hemorrhage
- 1987
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 76:2, s. 102-114
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary CNS amyloid angiopathy occurring in Icelanders is the first human disorder known to be caused by deposition of cystatin C amyloid fibrils in the walls of the brain arteries leading to single or or multiple strokes with fatal outcome. One or more affected members have been verified by histological examination in 8 families containing 127 affected. These originated from the same geographic area. Abnormally low value of cystatin C found in the cerebrospinal fluid of those affected can be used to support or make diagnosis of this disease, also in asymptomatic relatives. By amino acid sequence analysis the amyloid fibrils in the patients are found to be a variant of cystatin C (gamma-trace), a major cysteine proteinase inhibitor. The variant protein has an amino acid substitution (glutamine for leucine) at position 58 in the amyloid molecule. It is postulated that a point mutation has occurred leading to production of amyloidogenic protein causing the disorder.
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- Palsdottir, A, et al.
(författare)
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Mutation in cystatin C gene causes hereditary brain haemorrhage
- 1988
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Ingår i: The Lancet. - 1474-547X. ; 332:8611, s. 603-604
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disorder in which a cysteine proteinase inhibitor, cystatin C, is deposited as amyloid fibrils in the cerebral arteries of patients and leads to massive brain haemorrhage and death in young adults. A full length cystatin C cDNA probe revealed a mutation in the codon for leucine at position 68 which abolishes an Alu I restriction site in the cystatin C gene of HCCAA patients. The Alu I marker has been used to show that this mutation is transmitted only in affected members of all eight families investigated, and that the mutated cystatin C gene causes HCCAA.
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- Palsdottir, A, et al.
(författare)
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Mutation in the cystatin C gene causes hereditary brain hemorrhage
- 1989
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Ingår i: Progress in Clinical and Biological Research. - 0361-7742. ; 317, s. 241-246
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disorder leading to massive brain hemorrhage and death in young adults (Jensson et al., 1987). A variant of a potent inhibitor of cysteine proteinases, cystatin C (Barrett et al., 1984), is deposited as amyloid fibrils in the cerebral arteries of the patients (Ghiso et al., 1986). We have used the full length cystatin C cDNA probe (Abrahamson et al., 1987) to demonstrate a mutation in the codon for leucine at position 68, which abolishes an Alu I restriction site in cystatin C gene of the HCCAA patients. The Alu I marker has been used to show that this mutation is transmitted only in the affected members in all eight families investigated, proving that the mutated cystatin C gene causes HCCAA. This DNA marker will be useful for the diagnosis of HCCAA in patients, asymptomatic affected individuals and also for pre-natal diagnosis. HCCAA is the first human disorder known to be caused by an abnormal gene for a cysteine proteinase inhibitor
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- Palsdottir, A, et al.
(författare)
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Study of restriction fragment length polymorphism in the cystatin C gene of elderly patients with dementia and aged Down's syndrome patients
- 1989
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Ingår i: Progress in Clinical and Biological Research. - 0361-7742. ; 317, s. 235-239
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Tidskriftsartikel (refereegranskat)abstract
- Using a full length cystatin C cDNA probe and the Alu I restriction enzyme a total of 33 patients with senile dementia, Alzheimer type and 31 Down's syndrome patients have been investigated for the presence of the 630 bp Alu I restriction fragment length polymorphism in the cystatin C gene detected in Icelandic patients with hereditary cystatin C amyloid angiopathy. Results showed that all the patients had normal cystatin C fragment length of 600 bp.
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| 7. |
- Grubb, Anders, et al.
(författare)
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Immunohistochemical characterization of the amyloid deposits and quantitation of pertinent cerebrospinal fluid proteins in hereditary cerebral hemorrhage with amyloidosis
- 1987
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 18:2, s. 431-440
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Tidskriftsartikel (refereegranskat)abstract
- Cystatin C, a protein inhibitor of lysosomal cysteine proteinases, was demonstrated by immunohistochemical techniques to be present in the birefringent amyloid deposits of the small arteries in the cerebrum, cerebellum, and leptomeninges of 10 Icelandic individuals with hereditary cerebral hemorrhage with amyloidosis. Specimens from other organs were investigated in one of the patients, and amyloid angiopathy characterized by an immunoreactivity of cystatin C was found in a submandibular lymph node. No immunoreactivity of amyloid fibril protein AA, kappa or lambda immunoglobulin light chain, or prealbumin was observed. Significantly low cerebrospinal fluid concentrations of cystatin C were found in all 9 investigated individuals with hereditary cerebral hemorrhage with amyloidosis. The concentrations of beta 2-microglobulin, albumin, and IgG in the cerebrospinal fluid were within normal limits. Isoelectric focusing showed that cystatin C from the cerebrospinal fluid of 9 patients with hereditary cerebral hemorrhage with amyloidosis had an isoelectric point identical to that of normal individuals. This investigation demonstrates that hereditary cerebral hemorrhage with amyloidosis may be diagnosed by two laboratory methods: immunohistochemical investigation of cystatin C in brain tissue specimens and quantitation of cystatin C in cerebrospinal fluid.
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