NIPA1 mutation in complex hereditary spastic paraplegia with epilepsy
Article first published online: 22 FEB 2011
© 2011 The Author(s). European Journal of Neurology © 2011 EFNS
European Journal of Neurology
Volume 18, Issue 9, pages 1197–1199, September 2011
How to Cite
Svenstrup, K., Møller, R. S., Christensen, J., Budtz-Jørgensen, E., Gilling, M. and Nielsen, J. E. (2011), NIPA1 mutation in complex hereditary spastic paraplegia with epilepsy. European Journal of Neurology, 18: 1197–1199. doi: 10.1111/j.1468-1331.2011.03359.x
- Issue published online: 11 AUG 2011
- Article first published online: 22 FEB 2011
- Received 13 October 2010 Accepted 5 January 2011
- hereditary spastic paraplegia;
- idiopathic generalized epilepsy;
Background and purpose: Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurodegenerative disorders characterized in the ‘pure’ phenotype by progressive spasticity and weakness of the lower limbs. In the ‘complex’ phenotype, additional neurologic symptoms or signs are found. Mutations in the NIPA1 gene have been reported to cause spastic paraplegia type 6 (SPG6) in 10 families. SPG6 is a rare form of autosomal dominantly inherited HSP associated with a pure phenotype; however, in one complex SPG6 family, idiopathic generalized epilepsy (IGE) has been described and in addition, recurrent microdeletions at 15q11.2 including NIPA1 have been identified in patients with IGE. The purpose was to identify NIPA1 mutations in patients with pure and complex HSP.
Methods: Fifty-two patients with HSP were screened for mutations in NIPA1.
Results: One previously reported missense mutation c.316G>A, p.Gly106Arg, was identified in a complex HSP patient with spastic dysarthria, facial dystonia, atrophy of the small hand muscles, upper limb spasticity, and presumably IGE. The epilepsy co-segregated with HSP in the family.
Conclusion: NIPA1 mutations were rare in our population of patients with HSP, but can be found in patients with complex HSP. Epilepsy might be more common in SPG6 than in other forms of HSP because of a genetic risk factor closely linked to NIPA1.