PMID- 10391242
OWN - NLM
STAT- MEDLINE
DCOM- 19990721
LR  - 20161124
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 399
IP  - 6738
DP  - 1999 Jun 24
TI  - A stop-codon mutation in the BRI gene associated with familial British dementia.
PG  - 776-81
AB  - Familial British dementia (FBD), previously designated familial cerebral amyloid 
      angiopathy-British type, is an autosomal dominant disorder of undetermined origin
      characterized by progressive dementia, spasticity, and cerebellar ataxia, with
      onset at around the fifth decade of life. Cerebral amyloid angiopathy,
      non-neuritic and perivascular plaques and neurofibrillary tangles are the
      predominant pathological lesions. Here we report the identification of a unique
      4K protein subunit named ABri from isolated amyloid fibrils. This highly
      insoluble peptide is a fragment of a putative type-II single-spanning
      transmembrane precursor that is encoded by a novel gene, BRI, located on
      chromosome 13. A single base substitution at the stop codon of this gene
      generates a longer open reading frame, resulting in a larger, 277-residue
      precursor. Release of the 34 carboxy-terminal amino acids from the mutated
      precursor generates the ABri amyloid subunit. The mutation creates a cutting site
      for the restriction enzyme XbaI, which is useful for detecting asymptomatic
      carriers. Antibodies against the amyloid or homologous synthetic peptides
      recognize both parenchymal and vascular lesions in FBD patients. A point mutation
      at the stop codon of BRI therefore results in the generation of the ABri peptide,
      which is deposited as amyloid fibrils causing neuronal disfunction and dementia.
FAU - Vidal, R
AU  - Vidal R
AD  - Department of Pathology, New York University School of Medicine, New York 10016, 
      USA.
FAU - Frangione, B
AU  - Frangione B
FAU - Rostagno, A
AU  - Rostagno A
FAU - Mead, S
AU  - Mead S
FAU - Revesz, T
AU  - Revesz T
FAU - Plant, G
AU  - Plant G
FAU - Ghiso, J
AU  - Ghiso J
LA  - eng
SI  - GENBANK/AF152462
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Amyloid)
RN  - 0 (Codon, Terminator)
RN  - 0 (ITM2B protein, human)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Protein Precursors)
SB  - IM
MH  - Aged
MH  - Amino Acid Sequence
MH  - Amyloid/analysis/chemistry/*genetics
MH  - Animals
MH  - Base Sequence
MH  - Cerebral Amyloid Angiopathy/*genetics
MH  - Chromosomes, Human, Pair 13
MH  - Cloning, Molecular
MH  - Codon, Terminator/*genetics
MH  - Dementia/*genetics
MH  - Female
MH  - Humans
MH  - Membrane Glycoproteins
MH  - Membrane Proteins
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Pedigree
MH  - Protein Precursors/genetics
MH  - Sequence Homology, Amino Acid
MH  - United Kingdom
EDAT- 1999/07/03 10:00
MHDA- 2001/03/23 10:01
CRDT- 1999/07/03 10:00
PHST- 1999/07/03 10:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/07/03 10:00 [entrez]
AID - 10.1038/21637 [doi]
PST - ppublish
SO  - Nature. 1999 Jun 24;399(6738):776-81. doi: 10.1038/21637.