OBJECTIVES: The hereditary spastic paraplegias (HSP) are a genetically and clinically heterogeneous group of neurodegenerative disorders, mainly characterized by a progressive spasticity and weakness of the lower limbs. Mutations in the SPG4 and SPG3A genes are responsible for approximately 50% of autosomal dominant HSP. To genetically diagnose the Portuguese families with HSP, mutation analysis was performed for the SPG4 and SPG3A genes. PATIENTS AND METHODS: Analysis was performed by polymerase chain reaction, followed by denaturing high performance liquid chromatography (DHPLC), in 61 autosomal dominant (AD)-HSP families and 19 unrelated patients without family history. RESULTS: Ten novel mutations were identified: one in the SPG3A and nine in the SPG4 genes; three known mutations in the SPG4 were also found. Most of the novel mutations were frameshift or nonsense (80%), resulting in a dysfunctional protein. CONCLUSIONS: The SPG4 and SPG3A analysis allowed the identification of 10 novel mutations and the genetic diagnosis of approximately a quarter of our AD-HSP families.
OBJECTIVES: The hereditary spastic paraplegias (HSP) are a genetically and clinically heterogeneous group of neurodegenerative disorders, mainly characterized by a progressive spasticity and weakness of the lower limbs. Mutations in the SPG4 and SPG3A genes are responsible for approximately 50% of autosomal dominant HSP. To genetically diagnose the Portuguese families with HSP, mutation analysis was performed for the SPG4 and SPG3A genes. PATIENTS AND METHODS: Analysis was performed by polymerase chain reaction, followed by denaturing high performance liquid chromatography (DHPLC), in 61 autosomal dominant (AD)-HSP families and 19 unrelated patients without family history. RESULTS: Ten novel mutations were identified: one in the SPG3A and nine in the SPG4 genes; three known mutations in the SPG4 were also found. Most of the novel mutations were frameshift or nonsense (80%), resulting in a dysfunctional protein. CONCLUSIONS: The SPG4 and SPG3A analysis allowed the identification of 10 novel mutations and the genetic diagnosis of approximately a quarter of our AD-HSP families.
Authors: Xin Bian; Robin W Klemm; Tina Y Liu; Miao Zhang; Sha Sun; Xuewu Sui; Xinqi Liu; Tom A Rapoport; Junjie Hu Journal: Proc Natl Acad Sci U S A Date: 2011-02-22 Impact factor: 11.205
Authors: Tina Y Liu; Xin Bian; Sha Sun; Xiaoyu Hu; Robin W Klemm; William A Prinz; Tom A Rapoport; Junjie Hu Journal: Proc Natl Acad Sci U S A Date: 2012-07-16 Impact factor: 11.205
Authors: Tyler J Moss; Camilla Andreazza; Avani Verma; Andrea Daga; James A McNew Journal: Proc Natl Acad Sci U S A Date: 2011-06-20 Impact factor: 11.205
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
Authors: Mujahed I Mustafa; Naseem S Murshed; Abdelrahman H Abdelmoneim; Miyssa I Abdelmageed; Nafisa M Elfadol; Abdelrafie M Makhawi Journal: Scientifica (Cairo) Date: 2020-04-19