Novel SPG3A and SPG4 mutations in dominant spastic paraplegia families
Acta Neurol Scand 2009: 119: 113–118.
© 2008 The Authors Journal compilation © 2008 Blackwell Munksgaard. 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.
Document Type: Research Article
Affiliations: 1: UnIGENe, IBMC – Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal 2: Serviço de Neurologia, Hospital de São Sebastião, Feira, Portugal 3: ICBAS, Universidade do Porto, Portugal
Publication date: 01 February 2009