A novel PSEN2 mutation associated with a peculiar phenotype.
BACKGROUND
Mutations of presenilin 2 gene are a rare cause of familial Alzheimer disease (AD). We describe an Italian family with hereditary dementia associated with a novel mutation in the presenilin 2 gene.


METHODS
Clinical investigations of the diseased subjects; interviews with relatives; studies of medical records; pedigree analysis; and neuroradiologic, neuropathologic, and molecular genetic studies were carried out in the pedigree.


RESULTS
Genetic analysis showed a novel PSEN2 A85V mutation present in the proband and in all analyzed affected members, in a subject presenting with an amnesic mild cognitive impairment, and in a young, still asymptomatic subject. The proband showed a clinical phenotype indicative of Lewy body dementia and the neuropathologic examination demonstrated the presence of unusually abundant and widespread cortical Lewy bodies in addition to the hallmark lesions of AD. Other affected members exhibited a clinical phenotype typical of AD.


CONCLUSIONS
Our findings add complexity to the spectrum of atypical phenotypes associated with presenilin mutations and should then be taken into account when considering the nosography of neurodegenerative diseases. They also support previous data that specific mutations of genes associated with familial Alzheimer disease may influence the presence and extent of Lewy bodies.
Piscopo
P
P
Istituto Superiore di Sanità, 00161 Rome, Italy.
Marcon
G
G
Piras
M R
MR
Crestini
A
A
Campeggi
L Malvezzi
LM
Deiana
E
E
Cherchi
R
R
Tanda
F
F
Deplano
A
A
Vanacore
N
N
Tagliavini
F
F
Pocchiari
M
M
Giaccone
G
G
Confaloni
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D003704:Dementia / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D053766:Presenilin-2 / Q000235:genetics* / Q000378:metabolism
D053766:Presenilin-2