SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V. (21st May 2012)

• Record Type: Journal Article
• Authors: Sánchez‐Ferrero, E; Coto, E; Beetz, C; Gámez, J; Corao, AI; 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
• Is Part Of: Clinical genetics. Volume 83:Number 3(2013:Mar.)
• Page Start: 257
• Page End: 262
• Publication Date: 2012-05-21
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/j.1399-0004.2012.01896.x
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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. <italic>SPG7</italic> mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V.</p> <p>Mutations in the <italic>SPG7</italic> gene were initially reported in patients with autosomal recessive hereditary spastic paraplegia (HSP). Recent works suggested a dominant effect for some <italic>SPG7</italic> mutations. To characterize the <italic>SPG7</italic> mutational spectrum in a large cohort of Spanish HSP patients, we sequenced the whole <italic>SPG7</italic> gene in a total of 285 Spastic Paraplegia patients. Large gene rearrangements were also ascertained in some patients. We found a total of 14 <italic>SPG7</italic> 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 <italic>vs</italic> healthy controls (3% <italic>vs</italic> 1%), suggesting a pathogenic role for this <italic>SPG7</italic> variant. We reported a high frequency of patients with only one <italic>SPG7</italic> mutation, and a putative pathogenic role for the p.A510V variant.</p> </abstract>