Hereditary spastic paraplegia type 4 (SPG4): clinical and molecular-genetic characteristics

作者：Rudenskaya G E^*; Sermyagina I G; Illarioshkin S N; Sidorova O P; Fedotov V P; Polyakov A V

来源：Zhurnal Nevrologii i Psikhiatrii Imeni S S Korsakova, 2010, 110(6): 12-19.

• hereditary spastic paraplegia
• SPG4
• DNA diagnostics
• SPAST mutations
• phenotype

Hereditary spastic paraplegia (HSP), type 4, or SPG4, caused by various mutations in the spastin gene (SPAST) is the most common disorder in a heterogeneous group of autosomal dominant HSP's. We performed a search of SPAST mutations by routine methods (SSCP and subsequent direct sequencing of fragments with modified electrophoretic mobility) in a sample of 26 families with autosomal dominant HSP from different Russian regions. In six families, five of Russian and one of Tatar ethnicity, different SPAST mutations were detected. Three of the mutations, Arg431Stop, Gln280Arg FsX9 and Asn386Ser, were reported previously; the remaining three, Asp555Tyr, Thr369Thr and Asn184Thr, were novel. In the family with the Arg431Stop mutation, a linkage to SPG4 locus was also established, lod scores were 1,66 for D2S352 marker and 1,51 for D2S367. Another large family also showed a linkage to the SPG4 locus (lod scores 1,68 for D2S352 (sic) 2,17 for D2S367) but the mutation was not found which may be due to atypical SPAST mutations (large deletions etc) undetectable by routine methods of DNA analysis. Including this family, the proportion of the SPG4 in the sample is 27%, which is less than average literature data (40-45%). Most of our patients presented relatively late-onset "uncompicated" HSP, which was typical for SPG4, though different additional features in SPG4 patients were also known. One of our patients had very early-onset HSP and concomitant epilepsy. In two pedigrees, in which all available relatives were examined, some patients had mild signs of SPG4, even late in life.

• 出版日期2010