Novel SPG3A and SPG4 mutations in dominant spastic paraplegia families

Authors: Loureiro, J. L.; Miller-Fleming, L.¹; Thieleke-Matos, C.¹; Magalhães, P.¹; Cruz, V. T.²; Coutinho, P.; Sequeiros, J.³; Silveira, I.¹

Source: Acta Neurologica Scandinavica, Volume 119, Number 2, February 2009 , pp. 113-118(6)

Publisher: Wiley-Blackwell

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Abstract:

Loureiro JL, Miller-Fleming L, Thieleke-Matos C, Magalhães P, Cruz VT, Coutinho P, Sequeiros J, Silveira I. Novel SPG3A and SPG4 mutations in dominant spastic paraplegia families.

Acta Neurol Scand 2009: 119: 113-118.

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.

Keywords: atlastin-1; HSP; neurodegeneration; spastin; SPAST

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1600-0404.2008.01074.x

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: 2009-02-01

Novel SPG3A and SPG4 mutations in dominant spastic paraplegia families

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