MOLECULAR PATHOGENESIS OF SPINAL MUSCULAR ATROPHY

Project: Research project

Description

DESCRIPTION Spinal muscular atrophy (SMA) results from loss of both telomeric 5q13 copies of the SMN1 gene. The centromeric 5q13 SMN2 gene encodes an identical protein. While loss of SMN2 does not lead to development of SMA, the presence of SMN2 acts as a disease modifier in a dose-dependent manner. The SMN1 gene produces a full-length transcript while the primary product of SMN2 is an exon-skipped mRNA lacking exon 7. The principal investigator that a single non-polymorphic nucleotide difference between SMN1 and SMN2 is the basis for this alternative splicing. By comparing hybrid SMN genes derived from SMA patients with unaffected relatives, the principal investigator and his group demonstrated that the origin of this nucleotide (SMN1 or SMN2) dictated clinical outcome. Therefore, the clinical evolution of SMA correlates with the splicing of SMN genes. They have also reported that the SMN protein self-associates and the protein translated from the alternative spliced SMN2 RNA have a reduced ability to form oligomers. Furthermore, SMN point mutants from SMA patients show defective oligomerization proportional to their disease severity. These studies have defined the genetic and biochemical basis for development of SMA.
StatusFinished
Effective start/end date7/1/006/30/06

Funding

  • National Institutes of Health: $318,000.00
  • National Institutes of Health: $309,040.00
  • National Institutes of Health: $59,420.00
  • National Institutes of Health: $32,400.00
  • National Institutes of Health: $249,620.00
  • National Institutes of Health: $318,000.00
  • National Institutes of Health: $318,000.00

Fingerprint

Spinal Muscular Atrophy
Genes
Exons
Nucleotides
Research Personnel
Proteins
Aptitude
Alternative Splicing
Molecular Biology
RNA
Messenger RNA

ASJC

  • Medicine(all)
  • Neuroscience(all)