title: SPG5 and multiple sclerosis: clinical and genetic overlap?
abstract: BACKGROUND
  Autosomal recessive (AR) spastic paraplegia type 5 (SPG5) is due to mutations in the CYP7B1 gene, encoding for the cytochrome P450-7B1, responsible for oxysterols 7α-hydroxylation. Oxysterol/cholestenoic acids pool plays a role in motor neuron survival and immune response. SPG5 is characterized by white matter abnormalities at brain resonance imaging (MRI). In view of clinical presentation and MRI findings, multiple sclerosis (MS) is a possible differential diagnosis of SPG5. This study aimed to evaluate the frequency of CYP7B1 mutations in patients with MS.
  
  
  METHODS
  One hundred and seventeen MS patients with clinical spastic paraplegia or possible AR transmission were selected for the mutational screening.
  
  
  RESULTS
  Forty-three patients had primary progressive, 26 relapsing remitting, 26 secondary progressive, and 22 relapsing progressive MS clinical course. No CYP7B1 homozygous mutations were identified. Two novel variants and one pathogenic mutation were found at heterozygous state.
  
  
  CONCLUSIONS
  The two novel variants cosegregated with pyramidal signs and autoimmune diseases suggesting that they might be susceptibility factors. Reduced cytochrome P450-7B1 enzymatic activity could alter the balance among neurotoxic and neuroprotective oxysterols promoting motor neuron degeneration and/or immune response.
authors.affiliation: Department of Neurosciences, Reproductive Sciences and Odontostomatology, 'Federico II' University of Naples, Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Criscuolo
authors.affiliation: Department of Neurosciences, Reproductive Sciences and Odontostomatology, 'Federico II' University of Naples, Naples, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Carbone
authors.affiliation: Department of Neurosciences, Reproductive Sciences and Odontostomatology, 'Federico II' University of Naples, Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Lieto
authors.affiliation: Department of Neurosciences, Reproductive Sciences and Odontostomatology, 'Federico II' University of Naples, Naples, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Peluso
authors.affiliation: Department of Neurosciences, Reproductive Sciences and Odontostomatology, 'Federico II' University of Naples, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Guacci
authors.affiliation: Department of Neurosciences, Reproductive Sciences and Odontostomatology, 'Federico II' University of Naples, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Filla
authors.affiliation: Biostructure and Bioimaging Institute, National Research Council, Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Quarantelli
authors.affiliation: Department of Neurosciences, Reproductive Sciences and Odontostomatology, 'Federico II' University of Naples, Naples, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Lanzillo
authors.affiliation: Department of Neurosciences, Reproductive Sciences and Odontostomatology, 'Federico II' University of Naples, Naples, Italy.
authors.forename: V Brescia
authors.initials: VB
authors.lastname: Morra
authors.affiliation: Department of Neurosciences, Reproductive Sciences and Odontostomatology, 'Federico II' University of Naples, Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: De Michele
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology; D002648:Child; D000072474:Cytochrome P450 Family 7 / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D015419:Spastic Paraplegia, Hereditary / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D013250:Steroid Hydroxylases / Q000235:genetics*
chemical_list: D013250:Steroid Hydroxylases; D000072474:Cytochrome P450 Family 7; C499571:CYP7B1 protein, human
keywords: CYP7B1; SPG5; multiple sclerosis; spastic paraplegia