A decamer duplication in the 3' region of the BRI gene originates an amyloid peptide that is associated with dementia in a Danish kindred

Ruben Vidal, Tamas Révész, Agueda Rostagno, Eugene Kim, Janice L. Holton, Toke Bek, Marie Bojsen-Møller, Hans Braendgaard, Gordon Plant, Jorge Ghiso, Blas Frangione

Research output: Contribution to journalArticle

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Abstract

Familial Danish dementia (FDD), also known as heredopathia ophthalmo- oto-encephalica, is an autosomal dominant disorder characterized by cataracts, deafness, progressive ataxia, and dementia. Neuropathological findings include severe widespread cerebral amyloid angiopathy, hippocampal plaques, and neurofibrillary tangles, similar to Alzheimer's disease. N- terminal sequence analysis of isolated leptomeningeal amyloid fibrils revealed homology to ABri, the peptide originated by a point mutation at the stop codon of gene BRI in familial British dementia. Molecular genetic analysis of the BRI gene in the Danish kindred showed a different defect, namely the presence of a 10-nt duplication (795-796insTTTAATTTGT) between codons 265 and 266, one codon before the normal stop codon 267. The decamer duplication mutation produces a frame-shift in the BRI sequence generating a larger-than-normal precursor protein, of which the amyloid subunit (designated ADan) comprises the last 34 C-terminal amino acids. This de novo- created amyloidogenic peptide, associated with a genetic defect in the Danish kindred, stresses the importance of amyloid formation as a causative factor in neurodegeneration and dementia.

Original languageEnglish (US)
Pages (from-to)4920-4925
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number9
DOIs
StatePublished - Apr 25 2000
Externally publishedYes

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Terminator Codon
Amyloid
Codon
Dementia
Abrus
Cerebral Amyloid Angiopathy
Peptides
Neurofibrillary Tangles
Amyloid beta-Protein Precursor
Point Mutation
Genes
Sequence Analysis
Molecular Biology
Alzheimer Disease
Amino Acids
Mutation
Familial Danish dementia
Familial British Dementia
Cataract ataxia deafness

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

A decamer duplication in the 3' region of the BRI gene originates an amyloid peptide that is associated with dementia in a Danish kindred. / Vidal, Ruben; Révész, Tamas; Rostagno, Agueda; Kim, Eugene; Holton, Janice L.; Bek, Toke; Bojsen-Møller, Marie; Braendgaard, Hans; Plant, Gordon; Ghiso, Jorge; Frangione, Blas.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 9, 25.04.2000, p. 4920-4925.

Research output: Contribution to journalArticle

Vidal, Ruben ; Révész, Tamas ; Rostagno, Agueda ; Kim, Eugene ; Holton, Janice L. ; Bek, Toke ; Bojsen-Møller, Marie ; Braendgaard, Hans ; Plant, Gordon ; Ghiso, Jorge ; Frangione, Blas. / A decamer duplication in the 3' region of the BRI gene originates an amyloid peptide that is associated with dementia in a Danish kindred. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 9. pp. 4920-4925.
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