title: CYP7B1: novel mutations and magnetic resonance spectroscopy abnormalities in hereditary spastic paraplegia type 5A.
abstract: 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).
  
  
  CONCLUSIONS
  SPG5A could be characterized as a predominantly pure HSP. MRS showing elevated mI/Cr ratio in the white matter may be indicative of SPG5A.
authors.affiliation: Memory Disorders Research Group, Department of Neurology, Neurogenetics Clinic, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Roos
authors.forename: K
authors.initials: K
authors.lastname: Svenstrup
authors.forename: E R
authors.initials: ER
authors.lastname: Danielsen
authors.forename: C
authors.initials: C
authors.lastname: Thomsen
authors.forename: J E
authors.initials: JE
authors.lastname: Nielsen
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D000072474:Cytochrome P450 Family 7; D004252:DNA Mutational Analysis; D019054:Evoked Potentials, Motor; D005073:Evoked Potentials, Somatosensory; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008875:Middle Aged; D009154:Mutation; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology; D009431:Neural Conduction / Q000502:physiology; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D013250:Steroid Hydroxylases / Q000235:genetics*; D055815:Young Adult
chemical_list: D013250:Steroid Hydroxylases; D000072474:Cytochrome P450 Family 7; C499571:CYP7B1 protein, human
keywords: CYP7B1; MR spectroscopy; SPG5A; hereditary spastic paraplegia; magnetic resonance imaging