Expansion of the phenotypic spectrum of SPG6 caused by mutation in NIPA1.

Background: Hereditary spastic paraplegia type 6 (SPG6) is caused by mutations in the NIPA1 gene, this is a rare cause of HSP, until now, all the affected individuals reported displayed "pure" spastic paraplegia.

Objective: To analyze the genotype/phenotype correlation of mutations so far described in NIPA1.

Methods: Eighty-six Chinese Han HSP patients were investigated for SPG6 mutations by direct sequencing of the NIPA1 gene.

Results: One heterozygous missense mutation c.316G>C/p.G106R was identified in a complicated form of ADHSP family with peripheral nerves disease, and SPG6 mutation in our sample accounted for 3.6% (1/28) of ADHSP families and 1.1% (1/86) of non-ARHSP patients who were negative for SPG4, SPG3A and SPG31 mutations.

Conclusions: We report the first complicated case of SPG6 in the world by the presence of peripheral neuropathy, which extends the phenotype initially described.