BACKGROUND: Hereditary spastic paraplegia (HSP) is a group of genetically heterogeneous disorders characterized by progressive spasticity of the lower limbs. Mutations in the SPG4 gene, which encodes spastin protein, are responsible for up to 45% of autosomal dominant cases. OBJECTIVE: To search for disease-causing mutations in a large series of Italian patients with HSP. DESIGN: Samples of DNA were analyzed by direct sequencing of all exons in SPG4. Samples from a subset of patients were also analyzed by direct sequencing of all exons in SPG3A, SPG6, SPG10, and SPG13. SETTING: Molecular testing facility in Italy. PATIENTS: Sixty unrelated Italian patients with pure (n = 50) and complicated (n = 10) HSP. MAIN OUTCOME MEASURES: Mutations in SPG4, SPG3A, SPG6, SPG10, and SPG13. RESULTS: We identified 12 different mutations, 8 of which were novel, in 13 patients. No mutations of any of the other HSP genes tested were found in 15 patients with sporadic pure HSP who did not have mutations in the SPG4 gene. CONCLUSIONS: The overall rate of mutation in the SPG4 gene within our sample was 22%, rising to 26% when only patients with pure HSP were considered. The negative result obtained in 15 patients without mutations in SPG4 in whom 4 other genes were analyzed (SPG3A, SPG6, SPG10, and SPG13) indicate that these genes are not frequently mutated in sporadic pure HSP.
BACKGROUND:Hereditary spastic paraplegia (HSP) is a group of genetically heterogeneous disorders characterized by progressive spasticity of the lower limbs. Mutations in the SPG4 gene, which encodes spastin protein, are responsible for up to 45% of autosomal dominant cases. OBJECTIVE: To search for disease-causing mutations in a large series of Italian patients with HSP. DESIGN: Samples of DNA were analyzed by direct sequencing of all exons in SPG4. Samples from a subset of patients were also analyzed by direct sequencing of all exons in SPG3A, SPG6, SPG10, and SPG13. SETTING: Molecular testing facility in Italy. PATIENTS: Sixty unrelated Italian patients with pure (n = 50) and complicated (n = 10) HSP. MAIN OUTCOME MEASURES: Mutations in SPG4, SPG3A, SPG6, SPG10, and SPG13. RESULTS: We identified 12 different mutations, 8 of which were novel, in 13 patients. No mutations of any of the other HSP genes tested were found in 15 patients with sporadic pure HSP who did not have mutations in the SPG4 gene. CONCLUSIONS: The overall rate of mutation in the SPG4 gene within our sample was 22%, rising to 26% when only patients with pure HSP were considered. The negative result obtained in 15 patients without mutations in SPG4 in whom 4 other genes were analyzed (SPG3A, SPG6, SPG10, and SPG13) indicate that these genes are not frequently mutated in sporadic pure HSP.
Authors: Fang Du; Emily F Ozdowski; Ingrid K Kotowski; Douglas A Marchuk; Nina Tang Sherwood Journal: Hum Mol Genet Date: 2010-02-13 Impact factor: 6.150
Authors: Francisco Grandas; Manuel Desco; Francisco J Navas-Sánchez; Alberto Fernández-Pena; Daniel Martín de Blas; Yasser Alemán-Gómez; Luís Marcos-Vidal; Juan A Guzmán-de-Villoria; Pilar Fernández-García; Julia Romero; Irene Catalina; Laura Lillo; José L Muñoz-Blanco; Andrés Ordoñez-Ugalde; Beatriz Quintáns; Julio Pardo; María-Jesús Sobrido; Susanna Carmona Journal: J Neurol Date: 2021-01-28 Impact factor: 4.849
Authors: Victoria Alvarez; Elena Sánchez-Ferrero; Christian Beetz; Marta Díaz; Belén Alonso; Ana I Corao; Josep Gámez; Jesús Esteban; Juan F Gonzalo; Samuel I Pascual-Pascual; Adolfo López de Munain; Germán Moris; Renne Ribacoba; Celedonio Márquez; Jordi Rosell; Rosario Marín; Maria J García-Barcina; Emilia Del Castillo; Carmen Benito; Eliecer Coto Journal: BMC Neurol Date: 2010-10-08 Impact factor: 2.474