Portal de Periódicos da CAPES

Novel SPG3A and SPG4 mutations in dominant spastic paraplegia families

2008; Wiley; Volume: 119; Issue: 2 Linguagem: Inglês

10.1111/j.1600-0404.2008.01074.x

1600-0404

José L. Loureiro, Leonor Miller‐Fleming, Carolina Thieleke‐Matos, Paula Magalhães, Vítor Tedim Cruz, Paula Coutinho, Jorge Sequeiros, Isabel Silveira,

Genetic Neurodegenerative Diseases

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.