caa a22 4500 39757374X CHVBK 20180308164849.0 cr unu---uuuuu 161202e199607 xx s 000 0 eng 10.1093/hmg/5.7.985 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.7.985 Alzheimer's Disease Associated with Mutations in Presenilin 2 is Rare and Variably Penetrant [Elektronische Daten] [R. Sherrington, S. Froelich, S. Sorbi, D. Campion, H. Chi, E. A. Rogaeva, G. Levesque, E. I. Rogaev, C. Lin, Y. Liang, M. Ikeda, L. Mar, A. Brice, Y. Agid, M.E. Percy, F. Clerget-Darpoux, S. Piacentini, G. Marcon, B. Nacmias, L. Amaducci, T. Frebourg, L. Lannfelt, J. M. Rommens, P. H. St George-Hyslop] Missense mutations in the presenilin 2 (PS-2) gene on chromosome 1 were sought by direct nucleotide sequence analysis of the open reading frame of 60 pedigrees with familial Alzheimer's disease (FAD). In the majority of these pedigrees, PS-1 and β-amyloid precursor protein (βAPP) gene mutations had been excluded. While no additional PS-2 pathogenic mutations were detected, four silent nucleotide substitutions and alternative splicing of nucleotides 1338-1340 (Glu325) were observed. Analysis of additional members of a pedigree known to segregate a Met239Val mutation in PS-2 revealed that the age of onset of symptoms is highly variable (range 45-88 years). This variability is not attributable to differences in ApoE genotypes. These results suggest (i) that, in contrast to mutations in PS-1, mutations in PS-2are a relatively rare cause of FAD; (ii) that other genetic or environmental factors modify the AD phenotype associated with PS-2 mutations; and (iii) that still other FAD susceptibility genes remain to be identified. © 1996 Oxford University Press Sherrington R. Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto; Department of Medicine, Division of Neurology, The Toronto Hospital, Toronto, Ontario M5S 1A8, Canada aut Froelich S. Karolinska Institute, Department of Clinical Neurosciences, Geriatric Medicine, Novum, KFC, 141 86 Huddinge, Sweden aut Sorbi S. Department of Neurology and Psychiatry, University of Florence, Viale Morgagni 65, Florence, Italy aut Campion D. Laboratoire de Genetique Moleculaire, CHU Rouen, 76031 Rouen, France aut Chi H. Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto; Department of Medicine, Division of Neurology, The Toronto Hospital, Toronto, Ontario M5S 1A8, Canada aut Rogaeva E. A. Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto; Department of Medicine, Division of Neurology, The Toronto Hospital, Toronto, Ontario M5S 1A8, Canada aut Levesque G. Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto; Department of Medicine, Division of Neurology, The Toronto Hospital, Toronto, Ontario M5S 1A8, Canada aut Rogaev E. I. Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto; Department of Medicine, Division of Neurology, The Toronto Hospital, Toronto, Ontario M5S 1A8, Canada aut Lin C. Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto; Department of Medicine, Division of Neurology, The Toronto Hospital, Toronto, Ontario M5S 1A8, Canada aut Liang Y. Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto; Department of Medicine, Division of Neurology, The Toronto Hospital, Toronto, Ontario M5S 1A8, Canada aut Ikeda M. Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto; Department of Medicine, Division of Neurology, The Toronto Hospital, Toronto, Ontario M5S 1A8, Canada aut Mar L. Department of Medical and Molecular Genetics, University of Toronto, and Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada aut Brice A. Department of Neurology, Hopital de la Salpetriere, and INSERM U289, 75013 Paris, France aut Agid Y. Department of Neurology, Hopital de la Salpetriere, and INSERM U289, 75013 Paris, France aut Percy M.E. Surrey Place Centre, Department of Obstetrics and Gynaecology and Dept. of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada aut Clerget-Darpoux F. INSERM U155, Chateau de Longchamp, 75016, Paris, France aut Piacentini S. Department of Neurology and Psychiatry, University of Florence, Viale Morgagni 65, Florence, Italy aut Marcon G. Department of Neurology, University of Udine, Udine, Italy aut Nacmias B. Department of Neurology and Psychiatry, University of Florence, Viale Morgagni 65, Florence, Italy aut Amaducci L. Department of Neurology and Psychiatry, University of Florence, Viale Morgagni 65, Florence, Italy aut Frebourg T. Laboratoire de Genetique Moleculaire, CHU Rouen, 76031 Rouen, France aut Lannfelt L. Karolinska Institute, Department of Clinical Neurosciences, Geriatric Medicine, Novum, KFC, 141 86 Huddinge, Sweden aut Rommens J. M. Department of Medical and Molecular Genetics, University of Toronto, and Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada aut St George-Hyslop P. H. Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto; Department of Medicine, Division of Neurology, The Toronto Hospital, Toronto, Ontario M5S 1A8, Canada aut Human Molecular Genetics Oxford University Press 5/7(1996-07), 985-988 0964-6906 5:7<985 1996 5 hmg https://doi.org/10.1093/hmg/5.7.985 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.7.985 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sherrington R. Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto; Department of Medicine, Division of Neurology, The Toronto Hospital, Toronto, Ontario M5S 1A8, Canada aut NATIONALLICENCE 700 1- Froelich S. Karolinska Institute, Department of Clinical Neurosciences, Geriatric Medicine, Novum, KFC, 141 86 Huddinge, Sweden aut NATIONALLICENCE 700 1- Sorbi S. Department of Neurology and Psychiatry, University of Florence, Viale Morgagni 65, Florence, Italy aut NATIONALLICENCE 700 1- Campion D. Laboratoire de Genetique Moleculaire, CHU Rouen, 76031 Rouen, France aut NATIONALLICENCE 700 1- Chi H. Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto; Department of Medicine, Division of Neurology, The Toronto Hospital, Toronto, Ontario M5S 1A8, Canada aut NATIONALLICENCE 700 1- Rogaeva E. A. Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto; Department of Medicine, Division of Neurology, The Toronto Hospital, Toronto, Ontario M5S 1A8, Canada aut NATIONALLICENCE 700 1- Levesque G. Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto; Department of Medicine, Division of Neurology, The Toronto Hospital, Toronto, Ontario M5S 1A8, Canada aut NATIONALLICENCE 700 1- Rogaev E. I. Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto; Department of Medicine, Division of Neurology, The Toronto Hospital, Toronto, Ontario M5S 1A8, Canada aut NATIONALLICENCE 700 1- Lin C. Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto; Department of Medicine, Division of Neurology, The Toronto Hospital, Toronto, Ontario M5S 1A8, Canada aut NATIONALLICENCE 700 1- Liang Y. Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto; Department of Medicine, Division of Neurology, The Toronto Hospital, Toronto, Ontario M5S 1A8, Canada aut NATIONALLICENCE 700 1- Ikeda M. Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto; Department of Medicine, Division of Neurology, The Toronto Hospital, Toronto, Ontario M5S 1A8, Canada aut NATIONALLICENCE 700 1- Mar L. Department of Medical and Molecular Genetics, University of Toronto, and Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada aut NATIONALLICENCE 700 1- Brice A. Department of Neurology, Hopital de la Salpetriere, and INSERM U289, 75013 Paris, France aut NATIONALLICENCE 700 1- Agid Y. Department of Neurology, Hopital de la Salpetriere, and INSERM U289, 75013 Paris, France aut NATIONALLICENCE 700 1- Percy M.E. Surrey Place Centre, Department of Obstetrics and Gynaecology and Dept. of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada aut NATIONALLICENCE 700 1- Clerget-Darpoux F. INSERM U155, Chateau de Longchamp, 75016, Paris, France aut NATIONALLICENCE 700 1- Piacentini S. Department of Neurology and Psychiatry, University of Florence, Viale Morgagni 65, Florence, Italy aut NATIONALLICENCE 700 1- Marcon G. Department of Neurology, University of Udine, Udine, Italy aut NATIONALLICENCE 700 1- Nacmias B. Department of Neurology and Psychiatry, University of Florence, Viale Morgagni 65, Florence, Italy aut NATIONALLICENCE 700 1- Amaducci L. Department of Neurology and Psychiatry, University of Florence, Viale Morgagni 65, Florence, Italy aut NATIONALLICENCE 700 1- Frebourg T. Laboratoire de Genetique Moleculaire, CHU Rouen, 76031 Rouen, France aut NATIONALLICENCE 700 1- Lannfelt L. Karolinska Institute, Department of Clinical Neurosciences, Geriatric Medicine, Novum, KFC, 141 86 Huddinge, Sweden aut NATIONALLICENCE 700 1- Rommens J. M. Department of Medical and Molecular Genetics, University of Toronto, and Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada aut NATIONALLICENCE 700 1- St George-Hyslop P. H. Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto; Department of Medicine, Division of Neurology, The Toronto Hospital, Toronto, Ontario M5S 1A8, Canada aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/7(1996-07), 985-988 0964-6906 5:7<985 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford