Familial Alzheimer's disease co-segregates with a Met146I1e substitution in presenilin-1

Poul Jørgensen, Claus Bus, Niels Pallisgaard, Marianne Bryder, Arne Lund Jorgensen*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

Abstract

The presenilin-1 (PS-1)/S gene at chromosome 14q24.3 is, when mutated, the most common disease gene in autosomal dominant early-onset Alzheimer's disease. Substitution of methionine 146 of the gene product for either valine or leucine co-segregates with Alzheimer's disease with the age of onset in the late thirties or early forties. Here we describe a new substitution of methionine 146 for isoleucine that co-segregates with Alzheimer's disease with age of the onset in the early forties. All identified missense mutations in methionine codon 146 replace one hydrophobic amino acid (Met) with another (Val, Leu, Ile) and correspond to any nucleotide change at the first or third position of the codon. Second position mutations invariably lead to replacement of the hydrophobic methionine with a hydrophilic amino acid that may severely affect the function of the protein. The fact that no second position mutations have been identified so far may support the hypothesis that the protein product of PS-1 plays a crucial role during development.

Original languageEnglish
JournalClinical Genetics
Volume50
Issue number5
Pages (from-to)281-286
Number of pages6
ISSN0009-9163
DOIs
Publication statusPublished - Nov 1996
Externally publishedYes

Keywords

  • Alzheimer's disease
  • DNA sequence
  • Missense mutations
  • PCR
  • Presenilin-1

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