title: SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V.
abstract: 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.
authors.affiliation: Laboratory of Molecular Genetics-Genetic Unit, Laboratorio de Medicina, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Sánchez-Ferrero
authors.forename: E
authors.initials: E
authors.lastname: Coto
authors.forename: C
authors.initials: C
authors.lastname: Beetz
authors.forename: J
authors.initials: J
authors.lastname: Gámez
authors.forename: A I
authors.initials: AI
authors.lastname: Corao
authors.forename: M
authors.initials: M
authors.lastname: Díaz
authors.forename: J
authors.initials: J
authors.lastname: Esteban
authors.forename: E
authors.initials: E
authors.lastname: del Castillo
authors.forename: G
authors.initials: G
authors.lastname: Moris
authors.forename: J
authors.initials: J
authors.lastname: Infante
authors.forename: M
authors.initials: M
authors.lastname: Menéndez
authors.forename: S I
authors.initials: SI
authors.lastname: Pascual-Pascual
authors.forename: A
authors.initials: A
authors.lastname: López de Munaín
authors.forename: M J
authors.initials: MJ
authors.lastname: Garcia-Barcina
authors.forename: V
authors.initials: V
authors.lastname: Alvarez
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007223:Infant; D008666:Metalloendopeptidases / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D013030:Spain; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis / Q000235:genetics*; D055815:Young Adult
chemical_list: D008666:Metalloendopeptidases; C112889:SPG7 protein, human; D000074183:ATPases Associated with Diverse Cellular Activities