Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/8305
Title: Hereditary hepatic and systemic amyloidosis caused by a new deletion/insertion mutation in the apolipoprotein AI gene.
Author: Booth, David R.
Tan, Si-Yen
Booth, Sussanne E.
Tennent, Glenys A.
Hutchinson, Winston L.
Hsuan, J. Justin
Totty, Nicholas F.
Truong, Oanh
Soutar, Anne K.
Hawkins, Philip N.
Bruguera i Cortada, Miquel, 1942-
Caballeria Rovira, Joan
Solé, Manel
Campistol Plana, Josep M.
Pepys, Mark B.
Keywords: Amiloïdosi
Proteïnes
Fetge
Genètica molecular
Amyloidosis
Apolipoprotein AI
Gene
Liver
Mutation
Issue Date: 1996
Publisher: American Society for Clinical Investigation
Abstract: We report a Spanish family with autosomal-dominant non-neuropathic hereditary amyloidosis with a unique hepatic presentation and death from liver failure, usually by the sixth decade. The disease is caused by a previously unreported deletion/insertion mutation in exon 4 of the apolipoprotein AI (apoAI) gene encoding loss of residues 60-71 of normal mature apoAI and insertion at that position of two new residues, ValThr. Affected individuals are heterozygous for this mutation and have both normal apoAI and variant molecules bearing one extra positive charge, as predicted from the DNA sequence. The amyloid fibrils are composed exclusively of NH2-terminal fragments of the variant, ending mainly at positions corresponding to residues 83 and 92 in the mature wild-type sequence. Amyloid fibrils derived from the other three known amyloidogenic apoAI variants are also composed of similar NH2-terminal fragments. All known amyloidogenic apoAI variants carry one extra positive charge in this region, suggesting that it may be responsible for their enhanced amyloidogenicity. In addition to causing a new phenotype, this is the first deletion mutation to be described in association with hereditary amyloidosis and it significantly extends the value of the apoAI model for investigation of molecular mechanisms of amyloid fibrillogenesis.
Note: Reproducció del document publicat a http://dx.doi.org/10.1172/JCI118725
It is part of: Journal of Clinical Investigation, 1996, vol. 97, núm. 12, p. 2714¿2721.
URI: http://hdl.handle.net/2445/8305
ISSN: 0021-9738
Appears in Collections:Articles publicats en revistes (Fonaments Clínics)
Articles publicats en revistes (Medicina)

Files in This Item:
File Description SizeFormat 
122436.pdf378.31 kBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.