A gene for autosomal dominant juvenile amyotrophic lateral sclerosis (ALS4 ) localizes to a 500-kb interval on chromosome 9q34 (original) (raw)

ABSTRACT

Amyotrophic lateral sclerosis (ALS) denotes a heterogeneous group of neurodegenerative disorders affecting upper and lower motor neurons. ALS4 is a juvenile-onset, autosomal dominant form of ALS that is characterized by slow progression, distal limb weakness and amyotrophy, and pyramidal signs associated with severe loss of motor neurons in the brain and spinal cord. The ALS4 locus was recently mapped by linkage analysis to a large genetic interval on chromosome 9q34. By undertaking extensive genetic linkage analysis, we have significantly refined the ALS4 locus to a critical interval of less than 3 cM, flanked by D9S149 and D9S1198. Previous physical mapping in this region has indicated that this critical interval spans approximately 500 kb. Seventeen putative transcripts have been localized within this interval including 7 characterized genes, 2 partially characterized genes, and 8 "anonymous" expressed sequence tags . These are therefore positional candidate genes for the ALS4 locus. We have also undertaken mutation analysis and genetic mapping to investigate and exclude candidate genes, including RING3L/ORFX and RALGDS , from a pathogenic role in ALS4.

Access this article

Log in via an institution

Subscribe and save

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Author information

Authors and Affiliations

  1. Division of Genetics and Development, Department of Pediatrics, University of Washington, School of Medicine, Box 356320, 1959 NE Pacific Street, Seattle, WA 98195, USA, , , , , , US
    I. P. Blair, C. L. Bennett & P. F. Chance
  2. Neurogenetics Branch, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA, , , , , , US
    A. Abel & K. H. Fischbeck
  3. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA, , , , , , US
    B. A. Rabin, J. W. Griffin & D. R. Cornblath

Authors

  1. I. P. Blair
    You can also search for this author inPubMed Google Scholar
  2. C. L. Bennett
    You can also search for this author inPubMed Google Scholar
  3. A. Abel
    You can also search for this author inPubMed Google Scholar
  4. B. A. Rabin
    You can also search for this author inPubMed Google Scholar
  5. J. W. Griffin
    You can also search for this author inPubMed Google Scholar
  6. K. H. Fischbeck
    You can also search for this author inPubMed Google Scholar
  7. D. R. Cornblath
    You can also search for this author inPubMed Google Scholar
  8. P. F. Chance
    You can also search for this author inPubMed Google Scholar

Additional information

Received: December 28, 1999 / Accepted: February 29, 2000 / Published online: June 8, 2000

Rights and permissions

About this article

Cite this article

Blair, I., Bennett, C., Abel, A. et al. A gene for autosomal dominant juvenile amyotrophic lateral sclerosis (ALS4 ) localizes to a 500-kb interval on chromosome 9q34.Neurogenetics 3, 1–6 (2000). https://doi.org/10.1007/PL00022976

Download citation