|
Title
|
|
|
|
DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4)
| |
|
Author
|
|
|
|
| |
|
Abstract
|
|
|
|
| Juvenile amyotrophic lateral sclerosis (ALS4) is a rare autosomal dominant form of juvenile amyotrophic lateral sclerosis (ALS) characterized by distal muscle weakness and atrophy, normal sensation, and pyramidal signs. Individuals affected with ALS4 usually have an onset of symptoms at age <25 years, a slow rate of progression, and a normal life span. The ALS4 locus maps to a 1.7-Mb interval on chromosome 9q34 flanked by D9S64 and D9S1198. To identify the molecular basis of ALS4, we tested 19 genes within the ALS4 interval and detected missense mutations (T3I, L389S, and R2136H) in the Senataxin gene (SETX). The SETX gene encodes a novel 302.8-kD protein. Although its function remains unknown, SETX contains a DNA/RNA helicase domain with strong homology to human RENT1 and IGHMBP2, two genes encoding proteins known to have roles in RNA processing. These observations of ALS4 suggest that mutations in SETX may cause neuronal degeneration through dysfunction of the helicase activity or other steps in RNA processing. |
| |
|
Language
|
|
|
|
English
| |
|
Source (journal)
|
|
|
|
The American journal of human genetics / American Society of Human Genetics [Bethesda, Md] - New York, N.Y., 1949, currens
| |
|
Publication
|
|
|
|
New York, N.Y.
:
2004
| |
|
ISSN
|
|
|
|
0002-9297
[print]
1537-6605
[online]
| |
|
DOI
|
|
|
|
10.1086/421054
| |
|
Volume/pages
|
|
|
|
74
:6
(2004)
, p. 1128-1135
| |
|
ISI
|
|
|
|
000221651900006
| |
|
Full text (Publisher's DOI)
|
|
|
|
| |
|
Full text (open access)
|
|
|
|
| |
|