DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4).


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Chen, Y-Z; Bennett, CL; Huynh, HM; Blair, IP; Puls, I; Irobi, J; Dierick, I; Abel, A; Kennerson, ML; Rabin, BA; Nicholson, GA; Auer-Grumbach, M; Wagner, K; De Jonghe, P; Griffin, JW; Fischbeck, KH; Timmerman, V; Cornblath, DR; Chance, PF

Published Date

  • June 2004

Published In

Volume / Issue

  • 74 / 6

Start / End Page

  • 1128 - 1135

PubMed ID

  • 15106121

Pubmed Central ID

  • 15106121

International Standard Serial Number (ISSN)

  • 0002-9297

Digital Object Identifier (DOI)

  • 10.1086/421054


  • eng

Conference Location

  • United States