Hereditary cystatin C (γ-trace) amyloid angiopathy of the CNS causing cerebral hemorrhage
Corresponding Author
O. Jensson
The Blood Bank, Genetical Division, National Hospital, Reykjavik, Iceland.
*Dr. Olafur Jensson The Blood Bank National Hospital Reykjavik IcelandSearch for more papers by this authorG. Gudmundsson
Department of Neurology, National Hospital, Reykjavik, Iceland.
Search for more papers by this authorA. Arnason
The Blood Bank, Genetical Division, National Hospital, Reykjavik, Iceland.
Search for more papers by this authorH. Blöndal
Department of Pathology, National Hospital, Reykjavik, Iceland.
Search for more papers by this authorI. Petursdottir
The Blood Bank, Genetical Division, National Hospital, Reykjavik, Iceland.
Search for more papers by this authorL. Thorsteinsson
The Blood Bank, Genetical Division, National Hospital, Reykjavik, Iceland.
Search for more papers by this authorA. Grubb
Department of Clinical Chemistry, Malmö General Hospital, University of Lund, Sweden.
Search for more papers by this authorH. Löfberg
Department of Pathology, Malmö General Hospital, University of Lund, Sweden.
Search for more papers by this authorD. Cohen
Departments of Medicine and Pathology, New York University Medical Center, USA.
Search for more papers by this authorB. Frangione
Departments of Medicine and Pathology, New York University Medical Center, USA.
Search for more papers by this authorCorresponding Author
O. Jensson
The Blood Bank, Genetical Division, National Hospital, Reykjavik, Iceland.
*Dr. Olafur Jensson The Blood Bank National Hospital Reykjavik IcelandSearch for more papers by this authorG. Gudmundsson
Department of Neurology, National Hospital, Reykjavik, Iceland.
Search for more papers by this authorA. Arnason
The Blood Bank, Genetical Division, National Hospital, Reykjavik, Iceland.
Search for more papers by this authorH. Blöndal
Department of Pathology, National Hospital, Reykjavik, Iceland.
Search for more papers by this authorI. Petursdottir
The Blood Bank, Genetical Division, National Hospital, Reykjavik, Iceland.
Search for more papers by this authorL. Thorsteinsson
The Blood Bank, Genetical Division, National Hospital, Reykjavik, Iceland.
Search for more papers by this authorA. Grubb
Department of Clinical Chemistry, Malmö General Hospital, University of Lund, Sweden.
Search for more papers by this authorH. Löfberg
Department of Pathology, Malmö General Hospital, University of Lund, Sweden.
Search for more papers by this authorD. Cohen
Departments of Medicine and Pathology, New York University Medical Center, USA.
Search for more papers by this authorB. Frangione
Departments of Medicine and Pathology, New York University Medical Center, USA.
Search for more papers by this authorAbstract
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 (γ-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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