SPG5 HSP makes up about 5% of all HSP, and splits roughly 50-50 between pure and complicated forms. SPG5 HSPers can have widely varying symptoms.
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 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 HSP 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 extend the range of SPG5-related phenotypes and reveal variability in clinical presentation, disease course and functional profile in SPG5-related patients while providing clues for molecular diagnosis in cHSP.
SOURCE: Clin Genet. 2011 Jan 10.
Clinical phenotype variability in patients with hereditary spastic paraplegia type 5 associated with CYP7B1 mutations.
Arnoldi A, Crimella C, Tenderini E, Martinuzzi A, D’Angelo M, Musumeci O, Toscano A, Scarlato M, Fantin M, Bresolin N, Bassi M.
E. Medea Scientific Institute, Laboratory of Molecular Biology, Bosisio Parini, Lecco E. Medea Scientific Institute, Conegliano Research Center, Conegliano E. Medea Scientific Institute, Neuromuscular and Neurorehabilitation Unit, Bosisio Parini Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, Messina Department of Neurology, Institute of Experimental Neurology (INSpe), San Raffaele Scientific Institute, Milan Dino Ferrari Center, IRCCS Ca’ Granda Foundation Ospedale Maggiore Policlinico, Department of Neurological Sciences, Università di Milano, Milan, Italy.