title: Clinical phenotype variability in patients with hereditary spastic paraplegia type 5 associated with CYP7B1 mutations.
abstract: 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.
authors.affiliation: E. Medea Scientific Institute, Laboratory of Molecular Biology, Bosisio Parini, Lecco, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Arnoldi
authors.forename: C
authors.initials: C
authors.lastname: Crimella
authors.forename: E
authors.initials: E
authors.lastname: Tenderini
authors.forename: A
authors.initials: A
authors.lastname: Martinuzzi
authors.forename: M G
authors.initials: MG
authors.lastname: D'Angelo
authors.forename: O
authors.initials: O
authors.lastname: Musumeci
authors.forename: A
authors.initials: A
authors.lastname: Toscano
authors.forename: M
authors.initials: M
authors.lastname: Scarlato
authors.forename: M
authors.initials: M
authors.lastname: Fantin
authors.forename: N
authors.initials: N
authors.lastname: Bresolin
authors.forename: M T
authors.initials: MT
authors.lastname: Bassi
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D015331:Cohort Studies; D000072474:Cytochrome P450 Family 7; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016415:Sequence Alignment; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D013250:Steroid Hydroxylases / Q000235:genetics*
chemical_list: D013250:Steroid Hydroxylases; D000072474:Cytochrome P450 Family 7; C499571:CYP7B1 protein, human