Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (113)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Sherrington, R.
Right arrow Articles by St George-Hyslop, P. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sherrington, R.
Right arrow Articles by St George-Hyslop, P. H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, Vol 5, 985-988, Copyright © 1996 by Oxford University Press

ARTICLES

Alzheimer's disease associated with mutations in presenilin 2 is rare and variably penetrant

R Sherrington, S Froelich, S Sorbi, D Campion, H Chi, EA Rogaeva, G Levesque, EI Rogaev, C Lin, Y Liang, M Ikeda, L Mar, A Brice, Y Agid, ME Percy, F Clerget- Darpoux, S Piacentini, G Marcon, B Nacmias, L Amaducci, T Frebourg, L Lannfelt, JM Rommens and PH St George-Hyslop
Department of Medicine, University of Toronto, Ontario, Canada.

Missense mutations in the presenilin 2 (PS-2) gene on chromosome 1 were sought by direct nucleotide sequence analysis of the open reading frame of 60 pedigrees with familial Alzheimer's disease (FAD). In the majority of these pedigrees, PS-1 and beta-amyloid precursor protein (beta APP) gene mutations had been excluded. While no additional PS-2 pathogenic mutations were detected, four silent nucleotide substitutions and alternative splicing of nucleotides 1338-1340 (Glu325) were observed. Analysis of additional members of a pedigree known to segregate a Met239Val mutation in PS-2 revealed that the age of onset of symptoms is highly variable (range 45-88 years). This variability is not attributable to differences in ApoE genotypes. These results suggest (i) that, in contrast to mutations in PS-1, mutations in PS-2 are a relatively rare cause of FAD; (ii) that other genetic or environmental factor modify the AD phenotype associated with PS-2 mutations; and (iii) that still other FAD susceptibility genes remain to be identified.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
H. Steiner, R. Fluhrer, and C. Haass
Intramembrane Proteolysis by {gamma}-Secretase
J. Biol. Chem., October 31, 2008; 283(44): 29627 - 29631.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
P. Piscopo, G. Marcon, M. R. Piras, A. Crestini, L. M. Campeggi, E. Deiana, R. Cherchi, F. Tanda, A. Deplano, N. Vanacore, et al.
A novel PSEN2 mutation associated with a peculiar phenotype
Neurology, April 22, 2008; 70(17): 1549 - 1554.
[Abstract] [Full Text] [PDF]

Home page
 CMAJHome page
C. Patterson MD, J. W. Feightner MD MSc, A. Garcia MD PhD, G.-Y. R. Hsiung MD MHSc, C. MacKnight MD MSc, and A. D. Sadovnick PhD
Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease
Can. Med. Assoc. J., February 26, 2008; 178(5): 548 - 556.
[Abstract] [Full Text] [PDF]

Home page
 J Geriatr Psychiatry NeurolHome page
J. M. Ringman
What the Study of Persons At Risk for Familial Alzheimer's Disease Can Tell Us About the Earliest Stages of the Disorder: A Review
J Geriatr Psychiatry Neurol, December 1, 2005; 18(4): 228 - 233.
[Abstract] [PDF]

Home page
 NeurologyHome page
J. M. Ringman, C. Diaz-Olavarrieta, Y. Rodriguez, M. Chavez, L. Fairbanks, F. Paz, A. Varpetian, H. C. Maldonado, M. A. Macias-Islas, J. Murrell, et al.
Neuropsychological function in nondemented carriers of presenilin-1 mutations
Neurology, August 23, 2005; 65(4): 552 - 558.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
P. Mastrangelo, P. M. Mathews, M. A. Chishti, S. D. Schmidt, Y. Gu, J. Yang, M. J. Mazzella, J. Coomaraswamy, P. Horne, B. Strome, et al.
Dissociated phenotypes in presenilin transgenic mice define functionally distinct {gamma}-secretases
PNAS, June 21, 2005; 102(25): 8972 - 8977.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
J. L. Jankowsky, D. J. Fadale, J. Anderson, G. M. Xu, V. Gonzales, N. A. Jenkins, N. G. Copeland, M. K. Lee, L. H. Younkin, S. L. Wagner, et al.
Mutant presenilins specifically elevate the levels of the 42 residue {beta}-amyloid peptide in vivo: evidence for augmentation of a 42-specific {gamma} secretase
Hum. Mol. Genet., January 15, 2004; 13(2): 159 - 170.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Ris, I. Dewachter, D. Reverse, E. Godaux, and F. Van Leuven
Capacitative Calcium Entry Induces Hippocampal Long Term Potentiation in the Absence of Presenilin-1
J. Biol. Chem., November 7, 2003; 278(45): 44393 - 44399.
[Abstract] [Full Text] [PDF]

Home page
 Arch NeurolHome page
A. Tedde, B. Nacmias, M. Ciantelli, P. Forleo, E. Cellini, S. Bagnoli, C. Piccini, P. Caffarra, E. Ghidoni, M. Paganini, et al.
Identification of New Presenilin Gene Mutations in Early-Onset Familial Alzheimer Disease
Arch Neurol, November 1, 2003; 60(11): 1541 - 1544.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
O. Nyabi, M. Bentahir, K. Horre, A. Herreman, N. Gottardi-Littell, C. Van Broeckhoven, P. Merchiers, K. Spittaels, W. Annaert, and B. De Strooper
Presenilins Mutated at Asp-257 or Asp-385 Restore Pen-2 Expression and Nicastrin Glycosylation but Remain Catalytically Inactive in the Absence of Wild Type Presenilin
J. Biol. Chem., October 31, 2003; 278(44): 43430 - 43436.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
U. Finckh, A. Alberici, M. Antoniazzi, L. Benussi, V. Fedi, C. Giannini, A. Gal, R. M. Nitsch, and G. Binetti
Variable expression of familial Alzheimer disease associated with presenilin 2 mutation M239I
Neurology, May 23, 2000; 54(10): 2006 - 2008.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
E. Jaikaran, G Marcon, L Levesque, P. George-Hyslop, P. Fraser, and A Clark
Localisation of presenilin 2 in human and rodent pancreatic islet beta-cells; Met239Val presenilin 2 variant is not associated with diabetes in man
J. Cell Sci., January 7, 1999; 112(13): 2137 - 2144.
[Abstract] [PDF]

Home page
 Arch NeurolHome page
D. Blacker and R. E. Tanzi
The Genetics of Alzheimer Disease: Current Status and Future Prospects
Arch Neurol, March 1, 1998; 55(3): 294 - 296.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
G. Thinakaran, C. L. Harris, T. Ratovitski, F. Davenport, H. H. Slunt, D. L. Price, D. R. Borchelt, and S. S. Sisodia
Evidence That Levels of Presenilins (PS1 and PS2) Are Coordinately Regulated by Competition for Limiting Cellular Factors
J. Biol. Chem., November 7, 1997; 272(45): 28415 - 28422.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
S. Janicki and M. J. Monteiro
Increased Apoptosis Arising from Increased Expression of the Alzheimer's Disease-associated Presenilin-2 Mutation (N141I)
J. Cell Biol., October 20, 1997; 139(2): 485 - 495.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
C. L. Lendon, F. Ashall, and A. M. Goate
Exploring the Etiology of Alzheimer Disease Using Molecular Genetics
JAMA, March 12, 1997; 277(10): 825 - 831.
[Abstract] [PDF]

Home page
 JAMAHome page
S. G. Post, P. J. Whitehouse, R. H. Binstock, T. D. Bird, S. K. Eckert, L. A. Farrer, L. M. Fleck, A. D. Gaines, E. T. Juengst, H. Karlinsky, et al.
The Clinical Introduction of Genetic Testing for Alzheimer Disease: An Ethical Perspective
JAMA, March 12, 1997; 277(10): 832 - 836.
[Abstract] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.