Posted - June 2012 in Research Highlights
Wide spectrum of HSP forms
SPG7 mutations have now been shown to be inherited both dominantly and recessively, and to be associated with both pure and complicated HSP. This research study discovered 12 new SPG 7 mutations.
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.
SOURCE: Clinical Genetics. doi: 10.1111/j.1399-0004.2012.01896.x © 2012 John Wiley & Sons A/S
SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V
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
Laboratory of Molecular Genetics-Genetic Unit, Laboratorio de Medicina, Hospital Universitario Central de Asturias, 33006-Oviedo, Spain.