Clinical phenotype variability in patients with hereditary spastic paraplegia type 5 associated with CYP7B1 mutations

A. Arnoldi, C. Crimella, E. Tenderini, A. Martinuzzi, M. G. D'Angelo, O. Musumeci, A. Toscano, M. Scarlato, M. Fantin, N. Bresolin, M. T. Bassi

Research output: Contribution to journalArticle


Spastic paraplegia type 5 (SPG5) is caused by mutations in CYP7B1, a gene encoding the cytochrome P-450 oxysterol 7-α-hydroxylase, CYP7B1, an enzyme implicated in the cholesterol metabolism. Mutations in CYP7B1 were found in both pure and complicated forms of the disease with a mutation frequency of 7.7% in pure recessive cases. The mutation frequency in complex forms, approximately 6.6%, is more controversial and needs to be refined. We studied in more detail the SPG5-related spectrum of complex phenotypes by screening CYPB1 for mutations in a large cohort of 105 Italian hereditary spastic paraplegias (HSPs) index patients including 50 patients with a complicated HSP (cHSP) phenotype overlapping the SPG11- and the SPG15-related forms except for the lack of thin corpus callosum and 55 pure patients. Five CYP7B1 mutations, three of which are novel, were identified in four patients, two with a complex form of the disease and two with a pure phenotype. The CYP7B1 mutation frequencies obtained in both complicated and pure familial cases are comparable to the known ones. These results obtained extend the range of SPG5-related phenotypes and reveal variability in clinical presentation, disease course and functional profile in the SPG5-related patients while providing with some clues for molecular diagnosis in cHSP.

Original languageEnglish
Pages (from-to)150-157
Number of pages8
JournalClinical Genetics
Issue number2
Publication statusPublished - Feb 2012


  • Cholesterol metabolism
  • Complex HSP phenotype
  • CYP7B1
  • Mutation

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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