A novel presenilin 1 L166H mutation in a pseudo-sporadic case of early-onset Alzheimer's disease.
We report a 44-year-old woman presenting at 33 years with memory loss, followed by progressive dementia. Her family history was negative for dominant genetic disorders at high penetrance. Analysis of presenilin-1 gene revealed a missense mutation at codon 166, leading to the substitution from leucine to histidine. The mutation occurs in the third transmembrane domain of presenilin-1, at the position of two different mutations previously described, associated with an atypical phenotype. The present case has two implications: (1) mutations of presenilin-1 have to be searched also in apparently sporadic cases of dementia beginning in the third decade of life; (2) as yet unidentified factors, besides the gamma-secretase complex, influence the phenotype of presenilin-1 mutations.
Pantieri
R
R
Department of Neurosciences, Bellaria Hospital, Via Altura 3, I-40139 Bologna, Italy.
Pardini
M
M
Cecconi
M
M
Dagna-Bricarelli
F
F
Vitali
A
A
Piccini
A
A
Russo
R
R
Borghi
R
R
Tabaton
M
M
D000328:Adult; D000544:Alzheimer Disease / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D006639:Histidine / Q000235:genetics*; D006801:Humans; D007930:Leucine / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D053764:Presenilin-1
D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D006639:Histidine; D007930:Leucine