Clinical phenotype variability in patients with hereditary spastic paraplegia type 5 associated with CYP7B1 mutations
| Autor: | Alessia Arnoldi, Marianna Fantin, Claudia Crimella, Andrea Martinuzzi, Marina Scarlato, Antonio Toscano, Nereo Bresolin, M. T. Bassi, Erika Tenderini, Maria Grazia D'Angelo, Olimpia Musumeci |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Adult
Genotype CYP7B1 Hereditary spastic paraplegia Cytochrome P450 Family 7 Cholesterol metabolism Complex HSP phenotype Mutation Biology medicine.disease_cause Cohort Studies Genetics medicine Spastic Humans Genetic Predisposition to Disease Amino Acid Sequence Age of Onset Mutation frequency Genetics (clinical) Aged Base Sequence Spastic Paraplegia Hereditary Middle Aged medicine.disease Phenotype Pedigree Amino Acid Substitution Steroid Hydroxylases Age of onset Sequence Alignment |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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