title: NIPA1 gene mutations cause autosomal dominant hereditary spastic paraplegia (SPG6).
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.
mesh_terms: D001483:Base Sequence; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008958:Models, Molecular; D009154:Mutation; D010375:Pedigree; D017433:Protein Structure, Secondary; D012016:Reference Values; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C478824:NIPA1 protein, human