Two novel presenilin-1 mutations (Ser169Leu and Pro436Gln) associated with very early onset Alzheimer's disease

Kevin Taddei, John B.J. Kwok, Jillian J. Kril, Glenda M. Halliday, Helen Creasey, Marianne Hallupp, Christopher Fisher, William S. Brooks, Christopher Chung, Colin Andrews, Colin L. Masters, Peter R. Schofield, Ralph N. Martins*

*Corresponding author for this work

Research output: Contribution to journalArticle

39 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3335-3339
Number of pages5
JournalNeuroReport
Volume9
Issue number14
Publication statusPublished - 5 Oct 1998
Externally publishedYes

Keywords

  • Early onset Alzheimer's disease
  • Missense mutation
  • Presenilin genes

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