Most of the new mutations were frameshift or nonsense (80%), resulting in a dysfunctional protein.
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.
SOURCE: Acta Neurol Scand. 2008 Jul 29.
Novel SPG3A and SPG4 mutations in dominant spastic paraplegia families.
Loureiro JL, Miller-Fleming L, Thieleke-Matos C, Magalhães P, Cruz VT, Coutinho P, Sequeiros J, Silveira I.
UnIGENe, IBMC – Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal.