NIPA1 Gene Mutations Cause Autosomal Dominant Hereditary Spastic Paraplegia (SPG6)

Am J Hum Genet. 2003 Oct;73(4):967-71. doi: 10.1086/378817. Epub 2003 Sep 23.

Abstract

The hereditary spastic paraplegias (HSPs) are genetically heterogeneous disorders characterized by progressive lower-extremity weakness and spasticity. The molecular pathogenesis is poorly understood. We report discovery of a dominant negative mutation in the NIPA1 gene in a kindred with autosomal dominant HSP (ADHSP), linked to chromosome 15q11-q13 (SPG6 locus); and precisely the same mutation in an unrelated kindred with ADHSP that was too small for meaningful linkage analysis. NIPA1 is highly expressed in neuronal tissues and encodes a putative membrane transporter or receptor. Identification of the NIPA1 function and ligand will aid an understanding of axonal neurodegeneration in HSP and may have important therapeutic implications.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Female
  • Genes, Dominant
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Models, Molecular
  • Mutation*
  • Pedigree
  • Protein Structure, Secondary
  • Reference Values
  • Spastic Paraplegia, Hereditary / genetics*

Substances

  • Membrane Proteins
  • NIPA1 protein, human