Affiliations: [a] Institute of Human Genetics, Justus Liebig University, Giessen, Germany | [b] Gemeinschaftspraxis, Schlüchtern, Germany
Correspondence:
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Correspondence to: Dr. med. U. Müller, Institut für Humangenetik, Schlangenzahl 14, 35392 Giessen, Germany. Tel.: +49 641 99 41600; Fax: +49 641 99 41609; E-mail: [email protected].
Abstract: 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.
