| | |  | | | | Record from Web of Science® | | | | | | |
| SEGREGATION OF A MISSENSE MUTATION IN THE AMYLOID PRECURSOR PROTEIN GENE WITH FAMILIAL ALZHEIMERS-DISEASE |
|
|
| Author(s): GOATE A, CHARTIERHARLIN MC, MULLAN M, BROWN J, CRAWFORD F, FIDANI L, GIUFFRA L, HAYNES A, IRVING N, JAMES L, MANT R, NEWTON P, ROOKE K, ROQUES P, TALBOT C, PERICAKVANCE M, ROSES A, WILLIAMSON R, ROSSOR M, OWEN M, HARDY J |
| Source: NATURE Volume: 349 Issue: 6311 Pages: 704-706 Published: FEB 21 1991 |
| Times Cited: 2,394 References: 30 |
| Abstract: A LOCUS segregating with familial Alzheimer's disease (AD) has been mapped to chromosome 21 (ref. 1), close to the amyloid precursor protein (APP) gene 2-5. Recombinants between the APP gene and the AD locus have been reported 6-8 which seemed to exclude it as the site of the mutation causing familial AD. But recent genetic analysis of a large number of AD families has demonstrated that the disease is heterogeneous 9. Families with late-onset AD do not show linkage to chromosome 21 markers 9,10. Some families with early-onset AD show linkage to chromosome 21 markers, but some do not 8,9,11. This has led to the suggestion that there is non-allelic genetic heterogeneity even within early onset familial AD 8,9. To avoid problems that heterogeneity poses for genetic analysis, we have examined the cosegregation of AD and markers along the long arm of chromosome 21 in a single family with AD confirmed by autopsy. Here we demonstrate that in this kindred, which shows linkage to chromosome 21 markers, there is a point mutation in the APP gene. This mutation causes an amino-acid substitution (Val --> Ile) close to the carboxy terminus of the beta-amyloid peptide. Screening other cases of familial AD revealed a second unrelated family in which this variant occurs. This suggests that some cases of AD could be caused by mutations in the APP gene. |
| Document Type: Article |
| Language: English |
Addresses:
1. ST MARYS HOSP, SCH MED, DEPT BIOCHEM, ALZHEIMERS DIS RES GRP, LONDON W2 1PG, ENGLAND
2. ST MARYS HOSP, SCH MED, DEPT NEUROL, LONDON W2 1PG, ENGLAND
3. YALE UNIV, SCH MED, DEPT HUMAN GENET, NEW HAVEN, CT 06510 USA
4. DUKE UNIV, MED CTR, DURHAM, NC 27710 USA
5. UNIV COLL CARDIFF, DEPT PSYCHOL MED, CARDIFF CF4 4XN, S GLAM WALES
6. UNIV COLL CARDIFF, DEPT MED GENET, CARDIFF CF4 4XN, S GLAM WALES |
| Publisher: MACMILLAN MAGAZINES LTD, 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: EY627 |
| ISSN: 0028-0836 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |