Abstract for presentation at 11th International Congress of Human Genetics

Hereditary spastic paraplegia is frequently caused by mutations in a novel gene, SPG31

  • Stephan Züchner, Center for Human Genetics and Department of Psychiatry and Behavioral Science, Duke University Medical Center, Durham, NC, USA, United States
  • Gaofeng Wang, Center for Human Genetics, Duke University Medical Center, Durham, NC, USA, United States
  • Khan-Nhat Tran-Viet, Center for Human Genetics, Duke University Medical Center, Durham, NC, United States
  • Martha Nance, Park Nicollet Clinic, Minneapolis, MN, USA, United States
  • Perry Gaskell, Center for Human Genetics, Duke University Medical Center, Durham, NC, USA, United States
  • Allison Ashley-Koch, Center for Human Genetics, Duke University Medical Center, Durham, NC, USA, United States
  • Margaret Pericak-Vance, Center for Human Genetics, Duke University Medical Center, Durham, NC, USA, United States

    • Hereditary spastic paraplegia (HSP) comprise a group of clinically and genetically heterogeneous diseases that affect the upper motor neurons and their axonal projections. So far, 11 genes have been identified for autosomal dominant HSP with most of them being a rare cause. In two multigenerational families we have mapped a novel HSP locus (SPG31) on chromosome 2p12. By direct sequencing of candidate genes in the chromosomal area we identified two single-nucleotide deletions in a novel gene, SPG31. SPG31 belongs to a protein family of unknown function. In transfected cell lines we showed that different gene mutations caused significant disorganization of the microtubule network. In addition we screened index patients from 92 unselected HSP families and identified a total of five unique mutations that cosegregated with the disease phenotype and were not detected in 365 controls. One mutation occurred in a conserved micro RNA target site in the 3`-UTR of SPG31. We conclude that SPG31 accounts for about 5.5% of all HSP.

    Conference Organiser - ICMS Pty Ltd