Previously unrecognized missense mutation E126K of PSEN2 segregates with early onset Alzheimer's disease in a family.
Mutations in the gene PSEN2 are a rare cause of early onset Alzheimer's disease (EOAD). PSEN2 sequence variants are often only found in one patient and pathogenicity cannot be formally documented. Here we describe a previously unrecognized sequence change (c.376G>A) in PSEN2 in an EOAD patient and her likewise affected mother. This change results in the exchange of amino acid glutamic acid (E) by lysine (K) at position 126 of the protein (p.E126K). Pathogenicity of the mutation is shown by segregation with disease, evolutionary conservation of E126, and in silico analysis of the mutation.
Institute of Human Genetics, Justus Liebig University, Giessen, Germany.
Ulrich
U
Müller
Institute of Human Genetics, Justus Liebig University, Giessen, Germany.
Pia
P
Winter
Gemeinschaftspraxis, Schlüchtern, Germany.
Claus
C
Bolender
Institute of Human Genetics, Justus Liebig University, Giessen, Germany.
Dagmar
D
Nolte
D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D004252:DNA Mutational Analysis; D005190:Family; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D053766:Presenilin-2 / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
C508861:PSEN2 protein, human; D053766:Presenilin-2
Alzheimer's disease; E126K PSEN2 mutation; PSEN2; early onset Alzheimer disease; familial segregation