CYP7B1: novel mutations and magnetic resonance spectroscopy abnormalities in hereditary spastic paraplegia type 5A
| Autor: | Jørgen E. Nielsen, Kirsten Svenstrup, Peter Roos, Else Rubæk Danielsen, Carsten Thomsen |
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| Rok vydání: | 2013 |
| Předmět: |
In vivo magnetic resonance spectroscopy
Adult Pathology medicine.medical_specialty Magnetic Resonance Spectroscopy CYP7B1 Adolescent Hereditary spastic paraplegia DNA Mutational Analysis Cytochrome P450 Family 7 Neural Conduction medicine.disease_cause Nerve Fibers Myelinated Frameshift mutation White matter Cohort Studies Young Adult Evoked Potentials Somatosensory medicine Humans Mutation medicine.diagnostic_test business.industry Spastic Paraplegia Hereditary Brain Magnetic resonance imaging General Medicine Middle Aged medicine.disease Evoked Potentials Motor Magnetic Resonance Imaging Hyperintensity medicine.anatomical_structure Neurology Steroid Hydroxylases Female Neurology (clinical) business |
| Zdroj: | Acta neurologica Scandinavica. 129(5) |
| ISSN: | 1600-0404 |
| Popis: | The SPG5A subtype of Hereditary Spastic Paraplegia (HSP) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the CYP7B1 gene, which encodes a steroid cytochrome P450 7α-hydroxylase. This enzyme provides the primary metabolic route for neurosteroids. Clinically, SPG5A has been characterized as a pure form of HSP with a variable age of onset, but recently a broader spectrum of phenotypes has been described. Objective This study characterizes four unrelated SPG5A patients through clinical evaluation. Methods The investigations included blood biochemistry, electrophysiology, brain MRI and MR spectroscopy. Results One patient had saccadic pursuit eye movements in addition to a pure HSP phenotype. Motor evoked potential (MEP) examinations revealed prolonged central conduction time. MRI of the brain showed white matter hyperintensities (WMH) in one patient. MRS showed elevated mI/Cr ratio in white matter in two patients; in the one patient with WMH and in one patient with normal MRI. Four novel mutations were identified; one frameshift (c.509 delT p.L170fs), one premature stop codon (c.334 C>T p.R112X), one amino acid changing (c.440 G>A p.G147D) and one duplication (c.945_947 dupGGC p.A316AA). Conclusion SPG5A could be characterized as a predominantly pure HSP. MRS showing elevated mI/Cr ratio in the white matter may be indicative of SPG5A. |
| Databáze: | OpenAIRE |
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