title: Two novel presenilin-1 mutations (Ser169Leu and Pro436Gln) associated with very early onset Alzheimer's disease.
abstract: Mutations in the presenilin-1 (PS-1) gene account for the majority of early onset autosomal-dominant familial Alzheimer's disease (FAD) cases. We identified three missense mutations in the coding sequence of the PS-1 gene in three early onset (EO), FAD pedigrees. Alzheimer's disease was confirmed in one pedigree by autopsy. Mutation analysis of PCR products amplified from genomic DNA templates of affected individuals showed two novel mutations resulting in Ser169Leu and Pro436Gln and one known mutation resulting in Glu318Gly. The two new mutations are located within predicted transmembrane domains three (TM-3) and seven (TM-7), and are associated with a very early age of onset which is consistent with a marked loss of function of the protein. The age of onset in the pedigree with Glu318Gly mutation was similar to that reported previously in a separate pedigree with this mutation.
authors.affiliation: University of Western Australia, Department of Surgery, Hollywood Private Hospital, Nedlands.
authors.forename: K
authors.initials: K
authors.lastname: Taddei
authors.forename: J B
authors.initials: JB
authors.lastname: Kwok
authors.forename: J J
authors.initials: JJ
authors.lastname: Kril
authors.forename: G M
authors.initials: GM
authors.lastname: Halliday
authors.forename: H
authors.initials: H
authors.lastname: Creasey
authors.forename: M
authors.initials: M
authors.lastname: Hallupp
authors.forename: C
authors.initials: C
authors.lastname: Fisher
authors.forename: W S
authors.initials: WS
authors.lastname: Brooks
authors.forename: C
authors.initials: C
authors.lastname: Chung
authors.forename: C
authors.initials: C
authors.lastname: Andrews
authors.forename: C L
authors.initials: CL
authors.lastname: Masters
authors.forename: P R
authors.initials: PR
authors.lastname: Schofield
authors.forename: R N
authors.initials: RN
authors.lastname: Martins
mesh_terms: D000328:Adult; D017668:Age of Onset; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D004252:DNA Mutational Analysis; D005192:Family Health; D017809:Fatal Outcome; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation; D053764:Presenilin-1
chemical_list: D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1