| | |  | | | | Record from Web of Science® | | | | | | |
| MUTATIONS IN CU/ZN SUPEROXIDE-DISMUTASE GENE ARE ASSOCIATED WITH FAMILIAL AMYOTROPHIC-LATERAL-SCLEROSIS |
|
|
| Author(s): ROSEN DR, SIDDIQUE T, PATTERSON D, FIGLEWICZ DA, SAPP P, HENTATI A, DONALDSON D, GOTO J, OREGAN JP, DENG HX, RAHMANI Z, KRIZUS A, MCKENNAYASEK D, CAYABYAB A, GASTON SM, BERGER R, TANZI RE, HALPERIN JJ, HERZFELDT B, VANDENBERGH R, HUNG WY, BIRD T, DENG G, MULDER DW, SMYTH C, LAING NG, SORIANO E, PERICAKVANCE MA, HAINES J, ROULEAU GA, GUSELLA JS, HORVITZ HR, BROWN RH |
| Source: NATURE Volume: 362 Issue: 6415 Pages: 59-62 Published: MAR 4 1993 |
| Times Cited: 2,726 References: 47 |
| Abstract: AMYOTROPHIC lateral sclerosis (ALS) is a degenerative disorder of motor neurons in the cortex, brainstem and spinal cord1,2. Its cause is unknown and it is uniformly fatal, typically within five years3. About 10% of cases are inherited as an autosomal dominant trait, with high penetrance after the sixth decade4,5. In most instances, sporadic and autosomal dominant familial ALS (FALS) are clinically similar4,6,7. We have previously shown that in some but not all FALS pedigrees the disease is linked to a genetic defect on chromosome 21q (refs 8, 9). Here we report tight genetic linkage between FALS and a gene that encodes a cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), a homodimeric metalloenzyme that catalyzes the dismutation of the toxic superoxide anion O2.- to O2 and H2O2 (ref. 10). Given this linkage and the potential role of free radical toxicity in other neurodenegerative disorders11, we investigated SOD1 as a candidate gene in FALS. We identified 11 different SOD1 missense mutations in 13 different FALS families. |
| Document Type: Article |
| Language: English |
Addresses:
1. MASSACHUSETTS GEN HOSP, DAY NEUROMUSCULAR RES LAB, ROOM 6627, MGH-E, BLDG 149, 13TH ST, BOSTON, MA 02129 USA
2. NORTHWESTERN UNIV, SCH MED, DEPT NEUROL, CHICAGO, IL 60611 USA
3. ELEANOR ROOSEVELT INST CANC RES, DENVER, CO 80206 USA
4. UNIV COLORADO, HLTH SCI CTR, DENVER, CO 80206 USA
5. MCGILL UNIV, CTR RES NEUROSCI, MONTREAL H3A 2T5, QUEBEC CANADA
6. MONTREAL GEN HOSP, RES INST, MONTREAL H3G 1A4, QUEBEC CANADA
7. MIT, DEPT BIOL, HOWARD HUGHES MED INST, CAMBRIDGE, MA 02139 USA
8. MASSACHUSETTS GEN HOSP, CTR NEUROSCI, GENET & AGING LAB, BOSTON, MA 02129 USA
9. NORTHSHORE UNIV HOSP, DEPT NEUROL, MANHASSET, NY 11030 USA
10. UNIV ZIEKENHUIZEN, DEPT NEUROL, B-3000 LOUVAIN, BELGIUM
11. UNIV WASHINGTON, SCH MED, DEPT NEUROL, SEATTLE, WA 98195 USA
12. MAYO CLIN & MAYO FDN, DEPT NEUROL, ROCHESTER, MN 55905 USA
13. AUSTRALIAN NEUROMUSCULAR RES INST, NEDLANDS, WA AUSTRALIA
14. DUKE UNIV, MED CTR, DEPT MED NEUROL, DURHAM, NC 27710 USA
15. MASSACHUSETTS GEN HOSP, CTR NEUROSCI, MOLEC NEUROGENET LAB, BOSTON, MA 02129 USA |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: KP976 |
| ISSN: 0028-0836 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |