Posted - September 2011 in Research Highlights
SPG6 risk identified
Epilepsy might be more common in SPG6 than in other forms of HSP because of a genetic risk factor closely linked to the SPG6 HSP causing gene, NIPA1.
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.
Fifty-two patients with HSP were screened for mutations in NIPA1.
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.
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.
SOURCE: Eur J Neurol. 2011 Sep;18(9):1197-9. doi: 10.1111/j.1468-1331.2011.03359.x.
NIPA1 mutation in complex hereditary spastic paraplegia with epilepsy.
Section of Neurogenetics, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen Memory Disorders Research Group, Rigshospitalet, University Hospital of Copenhagen Department of Neurology, Danish Epilepsy Centre, Dianalund Department of Neurology, Aarhus University Hospital, Aarhus Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
© 2011 The Author(s). European Journal of Neurology © 2011 EFNS.