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. 1990 Dec 1;172(6):1865–1867. doi: 10.1084/jem.172.6.1865

Mutation in gelsolin gene in Finnish hereditary amyloidosis

PMCID: PMC2188742  PMID: 2175344

Abstract

Familial amyloidosis, Finnish type (FAF), is an autosomal dominant form of familial amyloid polyneuropathy. The novel amyloid fibril protein found in these patients is a degradation fragment of gelsolin, an actin- binding protein. We found a mutation (adenine for guanine) at nucleotide 654 of the gelsolin gene in genomic DNA isolated from five FAF patients. This site is polymorphic since the normal allele was also present in all the patients tested. This mutation was not found in two unaffected family members and 11 normal controls. The A for G transition causes an amino acid substitution (asparagine for aspartic acid) that was found at position 15 of the amyloid protein. The mutation and consequent amino acid substitution may lead to the development of FAF.

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Selected References

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  1. Boysen G., Galassi G., Kamieniecka Z., Schlaeger J., Trojaborg W. Familial amyloidosis with cranial neuropathy and corneal lattice dystrophy. J Neurol Neurosurg Psychiatry. 1979 Nov;42(11):1020–1030. doi: 10.1136/jnnp.42.11.1020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Darras B. T., Adelman L. S., Mora J. S., Bodziner R. A., Munsat T. L. Familial amyloidosis with cranial neuropathy and corneal lattice dystrophy. Neurology. 1986 Mar;36(3):432–435. doi: 10.1212/wnl.36.3.432. [DOI] [PubMed] [Google Scholar]
  3. Dwulet F. E., Benson M. D. Primary structure of an amyloid prealbumin and its plasma precursor in a heredofamilial polyneuropathy of Swedish origin. Proc Natl Acad Sci U S A. 1984 Feb;81(3):694–698. doi: 10.1073/pnas.81.3.694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Haltia M., Ghiso J., Prelli F., Gallo G., Kiuru S., Somer H., Palo J., Frangione B. Amyloid in familial amyloidosis, Finnish type, is antigenically and structurally related to gelsolin. Am J Pathol. 1990 Jun;136(6):1223–1228. [PMC free article] [PubMed] [Google Scholar]
  5. Haltia M., Prelli F., Ghiso J., Kiuru S., Somer H., Palo J., Frangione B. Amyloid protein in familial amyloidosis (Finnish type) is homologous to gelsolin, an actin-binding protein. Biochem Biophys Res Commun. 1990 Mar 30;167(3):927–932. doi: 10.1016/0006-291x(90)90612-q. [DOI] [PubMed] [Google Scholar]
  6. Hsiao K., Baker H. F., Crow T. J., Poulter M., Owen F., Terwilliger J. D., Westaway D., Ott J., Prusiner S. B. Linkage of a prion protein missense variant to Gerstmann-Sträussler syndrome. Nature. 1989 Mar 23;338(6213):342–345. doi: 10.1038/338342a0. [DOI] [PubMed] [Google Scholar]
  7. Johnstone E. M., Chaney M. O., Moore R. E., Ward K. E., Norris F. H., Little S. P. Alzheimer's disease amyloid peptide is encoded by two exons and shows similarity to soybean trypsin inhibitor. Biochem Biophys Res Commun. 1989 Sep 29;163(3):1248–1255. doi: 10.1016/0006-291x(89)91112-1. [DOI] [PubMed] [Google Scholar]
  8. Kwiatkowski D. J., Mehl R., Yin H. L. Genomic organization and biosynthesis of secreted and cytoplasmic forms of gelsolin. J Cell Biol. 1988 Feb;106(2):375–384. doi: 10.1083/jcb.106.2.375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kwiatkowski D. J., Stossel T. P., Orkin S. H., Mole J. E., Colten H. R., Yin H. L. Plasma and cytoplasmic gelsolins are encoded by a single gene and contain a duplicated actin-binding domain. Nature. 1986 Oct 2;323(6087):455–458. doi: 10.1038/323455a0. [DOI] [PubMed] [Google Scholar]
  10. Kwiatkowski D. J., Westbrook C. A., Bruns G. A., Morton C. C. Localization of gelsolin proximal to ABL on chromosome 9. Am J Hum Genet. 1988 Apr;42(4):565–572. [PMC free article] [PubMed] [Google Scholar]
  11. Levy E., Carman M. D., Fernandez-Madrid I. J., Power M. D., Lieberburg I., van Duinen S. G., Bots G. T., Luyendijk W., Frangione B. Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. Science. 1990 Jun 1;248(4959):1124–1126. doi: 10.1126/science.2111584. [DOI] [PubMed] [Google Scholar]
  12. Levy E., Lopez-Otin C., Ghiso J., Geltner D., Frangione B. Stroke in Icelandic patients with hereditary amyloid angiopathy is related to a mutation in the cystatin C gene, an inhibitor of cysteine proteases. J Exp Med. 1989 May 1;169(5):1771–1778. doi: 10.1084/jem.169.5.1771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Meretoja J. Familial systemic paramyloidosis with lattice dystrophy of the cornea, progressive cranial neuropathy, skin changes and various internal symptoms. A previously unrecognized heritable syndrome. Ann Clin Res. 1969 Dec;1(4):314–324. [PubMed] [Google Scholar]
  14. Meretoja J. Genetic aspects of familial amyloidosis with corneal lattice dystrophy and cranial neuropathy. Clin Genet. 1973;4(3):173–185. doi: 10.1111/j.1399-0004.1973.tb01140.x. [DOI] [PubMed] [Google Scholar]
  15. Prelli F., Levy E., van Duinen S. G., Bots G. T., Luyendijk W., Frangione B. Expression of a normal and variant Alzheimer's beta-protein gene in amyloid of hereditary cerebral hemorrhage, Dutch type: DNA and protein diagnostic assays. Biochem Biophys Res Commun. 1990 Jul 16;170(1):301–307. doi: 10.1016/0006-291x(90)91274-v. [DOI] [PubMed] [Google Scholar]
  16. Purcell J. J., Jr, Rodrigues M., Chishti M. I., Riner R. N., Dooley J. M. Lattice corneal dystrophy associated with familial systemic amyloidosis (Meretoja's syndrome). Ophthalmology. 1983 Dec;90(12):1512–1517. doi: 10.1016/s0161-6420(83)34369-4. [DOI] [PubMed] [Google Scholar]
  17. Sack G. H., Jr, Dumars K. W., Gummerson K. S., Law A., McKusick V. A. Three forms of dominant amyloid neuropathy. Johns Hopkins Med J. 1981 Dec;149(6):239–247. [PubMed] [Google Scholar]
  18. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  19. Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
  20. Way M., Weeds A. Nucleotide sequence of pig plasma gelsolin. Comparison of protein sequence with human gelsolin and other actin-severing proteins shows strong homologies and evidence for large internal repeats. J Mol Biol. 1988 Oct 20;203(4):1127–1133. doi: 10.1016/0022-2836(88)90132-5. [DOI] [PubMed] [Google Scholar]
  21. Winkelman J. E., Delleman J. W., Ansink B. J. Ein hereditäres Syndrom, bestehend aus peripherer Polyneuopatie, Hauveränderungen und gittriger Dystrophie der Hornhaut. Klin Monbl Augenheilkd. 1971 Nov;159(5):618–623. [PubMed] [Google Scholar]

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