SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V
Article first published online: 21 MAY 2012
© 2012 John Wiley & Sons A/S
Volume 83, Issue 3, pages 257–262, March 2013
How to Cite
Sánchez-Ferrero, E., Coto, E., Beetz, C., Gámez, J., Corao, A., Díaz, M., Esteban, J., del Castillo, E., Moris, G., Infante, J., Menéndez, M., Pascual-Pascual, S., López de Munaín, A., Garcia-Barcina, M. and Alvarez, V. (2013), SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V. Clinical Genetics, 83: 257–262. doi: 10.1111/j.1399-0004.2012.01896.x
- Issue published online: 18 FEB 2013
- Article first published online: 21 MAY 2012
- Accepted manuscript online: 10 MAY 2012 05:18AM EST
- Received 1 March 2012, revised and accepted for publication 1 May 2012
- hereditary spastic paraplegia;
Sánchez-Ferrero E, Coto E, Beetz C, Gámez J, Corao A, Díaz M, Esteban J, del Castillo E, Moris G, Infante J, Menéndez M, Pascual-Pascual SI, López de Munaín A, Garcia-Barcina MJ, Alvarez V on behalf of the Genetics of Spastic Paraplegia study group. SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V.
Mutations in the SPG7 gene were initially reported in patients with autosomal recessive hereditary spastic paraplegia (HSP). Recent works suggested a dominant effect for some SPG7 mutations. To characterize the SPG7 mutational spectrum in a large cohort of Spanish HSP patients, we sequenced the whole SPG7 gene in a total of 285 Spastic Paraplegia patients. Large gene rearrangements were also ascertained in some patients. We found a total of 14 SPG7 mutations (12 new) in 14 patients; 2 were large deletions. All the mutation carriers had an adult onset age but only five (35%) had a complicated phenotype. We identified a single mutation in 13 patients. Familial analysis suggested a dominant inheritance for one (p.Leu78*) of these mutations. Carriers of the rare p.A510V variant were significantly more frequent in patients vs healthy controls (3% vs 1%), suggesting a pathogenic role for this SPG7 variant. We reported a high frequency of patients with only one SPG7 mutation, and a putative pathogenic role for the p.A510V variant.