New V272A presenilin 1 mutation with very early onset subcortical dementia and parkinsonism.
In this report, we present the clinical and pathological details of a kindred of four individuals with a novel missense mutation (V272A) of the presenilin 1 gene (PSEN1) that experienced a subcortical dementia. The age of onset of symptoms ranged 26-36-year old, with an age at death of 36-46 years. Initial symptom was a marked mood disorder, with prominent parkinsonism in one case. The neuropsychological study, as well as the neuroimaging and PET in the proband were concordant with a subcortical dementia. The cerebral pathology showed in this patient, aside from the classical lesions of Alzheimer disease, Lewy bodies in cortex and substantia nigra, and widespread subcortical neuritic lesions. This clinical pattern and pathology expands the clinical spectrum of familial Alzheimer's disease and compel to include mutations of PSEN1 gene in the genetic study of subcortical dementia.
Hospital Ramon y Cajal, Universidad de Alcala, Madrid, Spain. adriano.jimenez@hrc.es
A
A
Jimenez-Escrig
A
A
Rabano
C
C
Guerrero
J
J
Simon
M S
MS
Barquero
I
I
Güell
R C
RC
Ginestal
T
T
Montero
L
L
Orensanz
D000328:Adult; D000409:Alanine / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000097:blood; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods; D003704:Dementia / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D005192:Family Health; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016631:Lewy Bodies; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016874:Neurofibrillary Tangles; D009483:Neuropsychological Tests; D020734:Parkinsonian Disorders / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood; D011180:Postmortem Changes; D053764:Presenilin-1; D051843:Synucleins; D014633:Valine / Q000235:genetics
D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; D051843:Synucleins; C075222:amyloid beta-protein (1-42); D014633:Valine; D000409:Alanine