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Studies on the Cystatin C Gene in Patients with Hereditary Cystatin C Amyloid Angiopathy (HCCAA) with Cerebral Haemorrhage

  • A. Palsdottir
  • O. Jensson
  • G. Gudmundsson
  • A. Arnason
  • M. Abrahamson
  • A. Grubb
  • I. Olafsson
  • A. Lundwall
Chapter

Abstract

Hereditary cystatin C amyloid angiopathy is a dominant disorder caused by the deposition of cystatin C in the brain arteries or arterioles of patients, leading to strokes at an early age.

The cystatin C gene in HCCAA patients was analysed to establish whether a marker for the disease could be found. A search for restriction fragment length polymorphism (RFLP) revealed a Sac I RFLP close to the 3′ end of the gene. The polymorphic fragments of 3.0 kb and 8.6 kb showed no correlation with the disease.

A DNA hybridization analysis was also performed on a reported Leu→Gln amino acid substitution in the amyloid cystatin C (1) using two allele-specific oligonucleotide probes corresponding to the normal leucine codon CTG (2) and the glutamine codon CAG. The oligonucleotide probes were hybridized to DNA sequences enzymatically amplified with cystatin C specific primers located on both sides of the reported mutation. The oligonucleotide probe corresponding to the normal sequence hybridized to all DNA samples, both from patients and healthy controls, while no hybridization signal was seen with the “mutant” probe.

The results suggest that the cystatin C gene is not closely linked to the gene causing the disease.

Keywords

Restriction Fragment Length Polymorphism Oligonucleotide Probe Amyloid Fibril Healthy Control Individual Human Insulin Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    J. Ghiso, O. Jensson and B. Frangione, Amyloid fibrils in hereditary cerebral hemorrhage with amyloidosis of Icelandic type is a variant of γ-trace basic protein, Proc. Natl. Acad. Sci. USA 83: 2974 (1986).CrossRefGoogle Scholar
  2. 2.
    M. Abrahamson, A. Grubb, I. Olafsson and A. Lundwall, Molecular cloning and sequence analysis of cDNA coding for the precursor of the human cysteine proteinase inhibitor cystatin C, FEBS Lett. 216: 229 (1987).CrossRefGoogle Scholar
  3. 3.
    O. Jensson, G. Gudmundsson, A. Arnason, H. Blöndal, I. Petursdottir, L. Thorsteinsson, A. Grubb, H. Löfberg, D. Cohen and B. Frangione, Hereditary cystatin C (γ-trace) amyloid angiopathy of the CNS causing cerebral hemorrhage, Acta Neurol. Scand. 76: 102 (1987).CrossRefGoogle Scholar
  4. 4.
    A. Grubb, O. Jensson, G. Gudmundsson, A. Arnason, H. Löfberg and J. Malm, Abnormal metabolism of γ-trace alkaline micro-protein. The basic defect in hereditary cerebral hemorrhage with amyloidosis, New Engl. J. Med. 311: 1547 (1984).CrossRefGoogle Scholar
  5. 5.
    G.I. Bell, J.H. Karam and W.J. Rutter, Polymorphic DNA region adjacent to the 5′ end of human insulin gene, Proc. Natl. Acad. Sci. USA 78: 5759 (1981).CrossRefGoogle Scholar
  6. 6.
    R.K. Saiki, T.L. Bugawan, G.T. Horn, K.G. Mullis and H.A. Erlich, Analysis of enzymatically amplified β-globin and HLA-DQ DNA with allele-specific oligonucleotide probes, Nature 324: 163 (1986).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • A. Palsdottir
    • 1
  • O. Jensson
    • 1
  • G. Gudmundsson
    • 2
  • A. Arnason
    • 1
  • M. Abrahamson
    • 3
    • 4
  • A. Grubb
    • 3
    • 4
  • I. Olafsson
    • 3
    • 4
  • A. Lundwall
    • 3
    • 4
  1. 1.The Blood BankUniversity of Lund, Malmö General HospitalMalmöSweden
  2. 2.Dept. of NeurologyUniversity of Lund, Malmö General HospitalMalmöSweden
  3. 3.National University HospitalReykjavikIceland
  4. 4.Dept. of Clinial ChemistryUniversity of Lund, Malmö General HospitalMalmöSweden

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