Two novel presenilin-1 mutations (Ser169Leu and Pro436Gln) associated with very early onset Alzheimer's disease

被引:48
作者
Taddei, K
Kwok, JBJ
Kril, JJ
Halliday, GM
Creasey, H
Hallupp, M
Fisher, C
Brooks, WS
Chung, C
Andrews, C
Masters, CL
Schofield, PR
Martins, RH
机构
[1] Sir James McCusker Alzheiers Dis Res Unit, Nedlands, WA 6009, Australia
[2] Univ Western Australia, Dept Surg, Hollywood Private Hosp, Nedlands, WA 6009, Australia
[3] Garvan Inst Med Res, Sydney, NSW 2010, Australia
[4] Univ Sydney, Ctr Educ & Res Aging, Concord, NSW 2139, Australia
[5] Concord Repatriat Gen Hosp, Concord, NSW 2139, Australia
[6] Prince Wales Med Res Inst, Randwick, NSW 2031, Australia
[7] Dept Rehabil & Aged Care, Joondalup, WA 6919, Australia
[8] Woden Valley Hosp, Woden, ACT 2606, Australia
[9] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia
关键词
early onset Alzheimer's disease; missense mutation; presenilin genes;
D O I
10.1097/00001756-199810050-00034
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
MUTATIONS in the presenilin-1 (PS-1) gene account for the majority of early onset autosomal-dominant familial Alzheimer's disease (FAD) cases. We identified three missense mutations in the coding sequence of the PS-1 gene in three early onset (EO), FAD pedigrees. Alzheimer's disease was confirmed in one pedigree by autopsy. Mutation analysis of PCR products amplified from genomic DNA templates of affected individuals showed two novel mutations resulting in Ser169Leu and Pro436Gln and one known mutation resulting in Glu318Gly. The two new mutations are located within predicted transmembrane domains three (TM-3) and seven (TM-7), and are associated with a very early age of onset which is consistent with a marked loss of function of the protein. The age of onset in the pedigree with Glu318Gly mutation was similar to that reported previously in a separate pedigree with this mutation. (C) 1998 Lippincott Williams & Wilkins.
引用
收藏
页码:3335 / 3339
页数:5
相关论文
共 30 条
[1]   Mutation analysis of presenilin 1 gene in Alzheimer's disease [J].
Boteva, K ;
Vitek, M ;
Mitsuda, H ;
deSilva, H ;
Xu, PT ;
Small, G ;
Gilbert, JR .
LANCET, 1996, 347 (8994) :130-131
[2]   A novel presenilin 1 mutation resulting in familial Alzheimer's disease with an onset age of 29 years [J].
Campion, D ;
Brice, A ;
Dumanchin, C ;
Puel, M ;
Baulac, M ;
delaSayette, V ;
Hannequin, D ;
Duyckaerts, C ;
Michon, A ;
Martin, C ;
Moreau, V ;
Penet, C ;
Martinez, M ;
ClergetDarpoux, F ;
Agid, Y ;
Frebourg, T .
NEUROREPORT, 1996, 7 (10) :1582-1584
[3]   MUTATIONS OF THE PRESENILIN-I GENE IN FAMILIES WITH EARLY-ONSET ALZHEIMERS-DISEASE [J].
CAMPION, D ;
FLAMAN, JM ;
BRICE, A ;
HANNEQUIN, D ;
DUBOIS, B ;
MARTIN, C ;
MOREAU, V ;
CHARBONNIER, F ;
DIDIERJEAN, O ;
TARDIEU, S ;
PENET, C ;
PUEL, M ;
PASQUIER, F ;
LEDOZE, F ;
BELLIS, G ;
CALENDA, A ;
HEILIG, R ;
MARTINEZ, M ;
MALLET, J ;
BELLIS, M ;
CLERGETDARPOUX, F ;
AGID, Y ;
FREBOURG, T .
HUMAN MOLECULAR GENETICS, 1995, 4 (12) :2373-2377
[4]   Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice [J].
Citron, M ;
Westaway, D ;
Xia, WM ;
Carlson, G ;
Diehl, T ;
Levesque, G ;
JohnsonWood, K ;
Lee, M ;
Seubert, P ;
Davis, A ;
Kholodenko, D ;
Motter, R ;
Sherrington, R ;
Perry, B ;
Yao, H ;
Strome, R ;
Lieberburg, I ;
Rommens, J ;
Kim, S ;
Schenk, D ;
Fraser, P ;
Hyslop, PS ;
Selkoe, DJ .
NATURE MEDICINE, 1997, 3 (01) :67-72
[5]   THE STRUCTURE OF THE PRESENILIN-1 (S182) GENE AND IDENTIFICATION OF 6 NOVEL MUTATIONS IN EARLY-ONSET AD FAMILIES [J].
CLARK, RF ;
HUTTON, M ;
FULDNER, RA ;
FROELICH, S ;
KARRAN, E ;
TALBOT, C ;
CROOK, R ;
LENDON, C ;
PRIHAR, G ;
HE, C ;
KORENBLAT, K ;
MARTINEZ, A ;
WRAGG, M ;
BUSFIELD, F ;
BEHRENS, MI ;
MYERS, A ;
NORTON, J ;
MORRIS, J ;
MEHTA, N ;
PEARSON, C ;
LINCOLN, S ;
BAKER, M ;
DUFF, K ;
ZEHR, C ;
PEREZTUR, J ;
HOULDEN, H ;
RUIZ, A ;
OSSA, J ;
LOPERA, F ;
ARCOS, M ;
MADRIGAL, L ;
COLLINGE, J ;
HUMPHREYS, C ;
ASHWORTH, A ;
SARNER, S ;
FOX, N ;
HARVEY, R ;
KENNEDY, A ;
ROQUES, P ;
CLINE, RT ;
PHILLIPS, CA ;
VENTER, JC ;
FORSELL, L ;
AXELMAN, K ;
LILIUS, L ;
JOHNSTON, J ;
COWBURN, R ;
VIITANEN, M ;
WINBLAD, B ;
KOSIK, K .
NATURE GENETICS, 1995, 11 (02) :219-222
[6]   MOLECULAR-GENETIC ANALYSIS OF FAMILIAL EARLY-ONSET ALZHEIMERS-DISEASE LINKED TO CHROMOSOME 14Q24.3 [J].
CRUTS, M ;
BACKHOVENS, H ;
WANG, SY ;
VANGASSEN, G ;
THEUNS, J ;
DEJONGHE, C ;
WEHNERT, A ;
DEVOECHT, J ;
DEWINTER, G ;
CRAS, P ;
BRUYLAND, M ;
DATSON, N ;
WEISSENBACH, J ;
DENDUNNEN, JT ;
MARTIN, JJ ;
HENDRIKS, L ;
Van Broeckhoven, C .
HUMAN MOLECULAR GENETICS, 1995, 4 (12) :2363-2371
[7]   Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population based study of presenile Alzheimer disease [J].
Cruts, M ;
van Duijn, CM ;
Backhovens, H ;
Van den Broeck, M ;
Wehnert, A ;
Serneels, S ;
Sherrington, R ;
Hutton, M ;
Hardy, J ;
St George-Hyslop, PH ;
Hofman, A ;
Van Broeckhoven, C .
HUMAN MOLECULAR GENETICS, 1998, 7 (01) :43-51
[8]  
daSilva HAR, 1997, NEUROREPORT, V8, pR1
[9]   Protein topology of presenilin 1 [J].
Doan, A ;
Thinakaran, G ;
Borchelt, DR ;
Slunt, HH ;
Ratovitsky, T ;
Podlisny, M ;
Selkoe, DJ ;
Seeger, M ;
Gandy, SE ;
Price, DL ;
Sisodia, SS .
NEURON, 1996, 17 (05) :1023-1030
[10]   MINI-MENTAL STATE - PRACTICAL METHOD FOR GRADING COGNITIVE STATE OF PATIENTS FOR CLINICIAN [J].
FOLSTEIN, MF ;
FOLSTEIN, SE ;
MCHUGH, PR .
JOURNAL OF PSYCHIATRIC RESEARCH, 1975, 12 (03) :189-198