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Novel SPG3A and SPG4 mutations in dominant spastic paraplegia families
Author(s) -
Loureiro J. L.,
MillerFleming L.,
ThielekeMatos C.,
Magalhães P.,
Cruz V. T.,
Coutinho P.,
Sequeiros J.,
Silveira I.
Publication year - 2009
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1111/j.1600-0404.2008.01074.x
Subject(s) - hereditary spastic paraplegia , genetics , frameshift mutation , genetic heterogeneity , mutation , gene , denaturing high performance liquid chromatography , spasticity , biology , medicine , phenotype , physical therapy
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.