title: Clinical and genetic findings in a series of Italian children with pure hereditary spastic paraplegia.
abstract: BACKGROUND
  hereditary spastic paraplegias (HSP) are a group of neurodegenerative disorders characterized by progressive lower extremity spastic weakness. SPG7, SPG4 and SPG3A are some of the autosomal genes recently found as mutated in recessive or dominant forms of HSP in childhood. SPG31 is more often associated with a pure spastic paraplegia phenotype, but genotype-phenotype correlation is still unclear. The aims of the current study was: (i) to verify the mutational frequency of SPG4, SPG3A, SPG31 and SPG7 genes in our very-well-selected childhood sample, and (ii) to improve our knowledge about the clinical and electrophysiological HSP phenotypes and their possible correlation with a specific mutation.
  
  
  METHODS
  a sample of 14 Italian children affected by pure HSP (mean age at diagnosis 5.9 years) was extensively investigated with electrophysiological, neuroradiological and genetic tests.
  
  
  RESULTS
  three SPG4 mutations were identified in three patients: two novel missense mutations, both sporadic, and one multiexonic deletion already reported. A novel large deletion in SPG31 gene involving exons 2-5 was also detected in one young patient. No mutations in the SPG7 and in the SPG3A genes were found.
  
  
  CONCLUSIONS
  our data confirm that HSP represent a heterogeneous group of genetic neurodegenerative disorders, also in sporadic or autosomal recessive early onset forms. Multiplex Ligation-dependent Probe Amplification-based mutation screening for SPG4 and SPG31 genes would be added to sequencing-based screening of SPG4, SPG31 and SPG3A genes in the routine diagnosis of HSP children.
authors.affiliation: Department of Developmental Neuroscience, IRCCS Stella Maris, Calambrone, Pisa, Italy. r.battini@inpe.unipi.it
authors.forename: R
authors.initials: R
authors.lastname: Battini
authors.forename: A
authors.initials: A
authors.lastname: Fogli
authors.forename: D
authors.initials: D
authors.lastname: Borghetti
authors.forename: A
authors.initials: A
authors.lastname: Michelucci
authors.forename: S
authors.initials: S
authors.lastname: Perazza
authors.forename: F
authors.initials: F
authors.lastname: Baldinotti
authors.forename: M E
authors.initials: ME
authors.lastname: Conidi
authors.forename: M I
authors.initials: MI
authors.lastname: Ferreri
authors.forename: P
authors.initials: P
authors.lastname: Simi
authors.forename: G
authors.initials: G
authors.lastname: Cioni
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics; D000293:Adolescent; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D019204:GTP-Binding Proteins; D017353:Gene Deletion; D005787:Gene Frequency; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008666:Metalloendopeptidases / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000503:physiopathology*; D000074181:Spastin
chemical_list: D008565:Membrane Proteins; D008666:Metalloendopeptidases; C112889:SPG7 protein, human; C440006:ATL1 protein, human; D000251:Adenosine Triphosphatases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D000074183:ATPases Associated with Diverse Cellular Activities; D000074181:Spastin; C400283:SPAST protein, human