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SPG5 and multiple sclerosis: clinical and genetic overlap?
Author(s) -
Criscuolo C.,
Carbone R.,
Lieto M.,
Peluso S.,
Guacci A.,
Filla A.,
Quarantelli M.,
Lanzillo R.,
Brescia Morra V.,
De Michele G.
Publication year - 2016
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1111/ane.12476
Subject(s) - multiple sclerosis , medicine , neuroscience , physical medicine and rehabilitation , psychology , psychiatry
Background Autosomal recessive (AR) spastic paraplegia type 5 ( SPG 5) is due to mutations in the CYP 7B1 gene, encoding for the cytochrome P450‐7B1, responsible for oxysterols 7 α ‐hydroxylation. Oxysterol/cholestenoic acids pool plays a role in motor neuron survival and immune response. SPG 5 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 SPG 5. This study aimed to evaluate the frequency of CYP 7B1 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 CYP 7B1 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.