Three novel presenilin 1 mutations marking the wide spectrum of age at onset and clinical patterns in familial Alzheimer's disease.
Presenilin 1 (PSEN1) mutations are the major cause of autosomal dominant Alzheimer's disease (ADAD). Here we report three novel PSEN1 mutations: Ile238_Lys239insIle, Ala246Pro and Ala164Val from patients who manifested in their twenties, forties and seventies, respectively, with variant clinical presentations of dementia. These cases exemplify the tremendous heterogeneity of clinical phenotypes and age of onset associated with PSEN1 mutations. The possibility of ADAD--not previously suspected in two of our patients--should always be considered in neurodegenerative conditions albeit they might neither exhibit the typical clinical picture of Alzheimer's disease nor early onset dementia, which is regarded the primary clinical sign of hereditary neurodegeneration.
Center for Neuropathology and Prion Research, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 23, 81377, Munich, Germany. Sigrun.Roeber@med.uni-muenchen.de.
Sigrun
S
Roeber
Department of Neurology, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany.|Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) e.V.- München, Feodor-Lynen-Strasse 17, 81377, Munich, Germany.
Felix
F
Müller-Sarnowski
Institute of Human Genetics, Justus-Liebig-Universität Giessen, Schlangenzahl 14, 35392, Giessen, Germany.
Julia
J
Kress
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) e.V.- München, Feodor-Lynen-Strasse 17, 81377, Munich, Germany.|Munich Cluster of Systems Neurology (SyNergy), Feodor-Lynen-Strasse 17, 81377, Munich, Germany.
Dieter
D
Edbauer
Institute for Neuropathology, University of Münster, Domagkstrasse 19, 48129, Münster, Germany.
Tanja
T
Kuhlmann
Institute of Human Genetics, University of Münster, Vesaliusweg 12-14, 48149, Münster, Germany.
Frank
F
Tüttelmann
Institute of Pathology, Klinikum Nürnberg Nord, Prof.-Ernst-Nathan-Strasse 1, 90419, Nuernberg, Germany.
Christoph
C
Schindler
Institute of Human Genetics, Justus-Liebig-Universität Giessen, Schlangenzahl 14, 35392, Giessen, Germany.
Pia
P
Winter
Center for Neuropathology and Prion Research, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 23, 81377, Munich, Germany.|Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) e.V.- München, Feodor-Lynen-Strasse 17, 81377, Munich, Germany.
Thomas
T
Arzberger
Institute of Human Genetics, Justus-Liebig-Universität Giessen, Schlangenzahl 14, 35392, Giessen, Germany.
Ulrich
U
Müller
Department of Neurology, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany.|Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) e.V.- München, Feodor-Lynen-Strasse 17, 81377, Munich, Germany.
Adrian
A
Danek
Center for Neuropathology and Prion Research, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 23, 81377, Munich, Germany.
Hans A
HA
Kretzschmar
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D053764:Presenilin-1 / Q000235:genetics*
C508853:PSEN1 protein, human; D053764:Presenilin-1
Alcoholism; Autosomal dominant Alzheimer’s disease (ADAD); Early onset Alzheimer’s disease (EOAD); PSEN1 mutation; Presenilin; Spastic paraparesis