SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V |
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| Authors: | E Sánchez‐Ferrero E Coto C Beetz J Gámez AI Corao M Díaz J Esteban E del Castillo G Moris J Infante M Menéndez SI Pascual‐Pascual A López de Munaín MJ Garcia‐Barcina V Alvarez |
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| Affiliation: | 1. Laboratory of Molecular Genetics‐Genetic Unit, Laboratorio de Medicina, Hospital Universitario Central de Asturias, Oviedo, Spain;2. Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Jena, Jena, Germany;3. Department of Neurology, Hospital Universitari Vall d'Hebron, VHIR Universidad Autonoma de Barcelona, Barcelona, Spain;4. Department of Neurology, Hospital 12 de Octubre, Madrid, Spain;5. Genetics Unit, Hospital Universitario Carlos Haya, Málaga, Spain;6. Department of Neurology, Hospital Universitario Central de Asturias, Oviedo, Spain;7. Department of Neurology, Hospital Universitario M de Valdecilla, Santander, Spain;8. Department of Neurology, Hospital Alvarez‐Buylla, Mieres, Spain;9. Department of Pediatric Neurology, University Hospital La Paz, Madrid, Spain;10. Department of Neurology, Hospital Donostia‐Instituto Biodonostia‐Ciberned, San Sebastián, Spain;11. Department of Genetics, Hospital de Basurto, Bilbao, Spain |
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| Abstract: | ![]()
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. |
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| Keywords: | hereditary spastic paraplegia mutation paraplegin |
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