title: A novel presenilin 1 L166H mutation in a pseudo-sporadic case of early-onset Alzheimer's disease.
abstract: 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.
authors.affiliation: Department of Neurosciences, Bellaria Hospital, Via Altura 3, I-40139 Bologna, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Pantieri
authors.forename: M
authors.initials: M
authors.lastname: Pardini
authors.forename: M
authors.initials: M
authors.lastname: Cecconi
authors.forename: F
authors.initials: F
authors.lastname: Dagna-Bricarelli
authors.forename: A
authors.initials: A
authors.lastname: Vitali
authors.forename: A
authors.initials: A
authors.lastname: Piccini
authors.forename: R
authors.initials: R
authors.lastname: Russo
authors.forename: R
authors.initials: R
authors.lastname: Borghi
authors.forename: M
authors.initials: M
authors.lastname: Tabaton
mesh_terms: 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
chemical_list: D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D006639:Histidine; D007930:Leucine