Candidate Gene for the Chromosome 1 Familial Alzheimer's Disease Locus

TLDR

STM2’s predicted amino acid sequence is homologous to the recently cloned chromosome 14 AD gene S182. The study identified STM2 as a candidate gene for the chromosome 1 AD locus and found a pathogenic N141L missense mutation conserved across species, supporting the hypothesis that mutations in both STM2 and the homologous S182 gene contribute to Alzheimer’s disease.

Abstract

A candidate gene for the chromosome 1 Alzheimer's disease (AD) locus was identified (STM2). The predicted amino acid sequence for STM2 is homologous to that of the recently cloned chromosome 14 AD gene (S182). A point mutation in STM2, resulting in the substitution of an isoleucine for an asparagine (N141l), was identified in affected people from Volga German AD kindreds. This N141l mutation occurs at an amino acid residue that is conserved in human S182 and in the mouse S182 homolog. The presence of missense mutations in AD subjects in two highly similar genes strongly supports the hypothesis that mutations in both are pathogenic.