Presenilin 1 Glu318Gly polymorphism: interpret with caution.
BACKGROUND
The significance of the presenilin 1 (PSEN1) Glu318Gly polymorphism has been described as either a causal mutation with reduced penetrance or a benign polymorphism. When this polymorphism is found in a symptomatic person with a family history of dementia, counseling on recurrence risk becomes very problematic.


OBJECTIVE
To demonstrate that the PSEN1 Glu318Gly polymorphism should be interpreted cautiously.


METHODS
Case histories of 2 patients with presenile dementia and family histories of dementia are described. The PSEN1 gene was sequenced in the patients and in 11 family members of patient 1.


RESULTS
Two patients with presenile dementia and personality change were found to carry the PSEN1 Glu318Gly polymorphism. The presence of the polymorphism was confirmed in several family members of patient 1 but was absent in 1 symptomatic relative.


CONCLUSIONS
The Glu318Gly polymorphism may be associated with risk for neurodegenerative disease; however, in the cases described here, it did not appear to be a risk factor. Until there is consensus on whether it is associated with disease, families should be informed that the clinical significance of the polymorphism is uncertain.
Goldman
Jill S
JS
Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA 94143-1207, USA. jgoldman@memory.ucsf.edu
Johnson
Julene K
JK
McElligott
Karen
K
Suchowersky
Oksana
O
Miller
Bruce L
BL
Van Deerlin
Vivianna M
VM
D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D005260:Female; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D010375:Pedigree; D011110:Polymorphism, Genetic; D053764:Presenilin-1; D012307:Risk Factors
D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1