Mutations in NIPA1 (non-imprinted in Prader-Willi/Angelman syndrome) have been described as a cause of autosomal dominant hereditary spastic paraplegia (HSP) known as SPG6 (spastic paraplegia-6).
Moreover, we demonstrated that HSP-causing mutations in both atlastin-1 and NIPA1 reduced axonal and dendritic sprouting in cultured rat cortical neurons.
We also developed PCR RFLP assays to detect recurrent NIPA1 changes and screened 101 independent HSP patients, including 45 index patients of autosomal dominant HSP families.
We conclude that NIPA1 normally encodes a Mg2+ transporter and the loss-of function of NIPA1(SPG6) due to abnormal trafficking of the mutated protein provides the basis of the HSP phenotype.
Mutations in NIPA1 (Nonimprinted in Prader-Willi/Angelman syndrome 1) have recently been identified as a cause of autosomal dominant pure HSP, with one mutation described in two unrelated families.
Identification of the NIPA1 function and ligand will aid an understanding of axonal neurodegeneration in HSP and may have important therapeutic implications.