SPG5 and multiple sclerosis: clinical and genetic overlap?
| Autor: | Maria Lieto, V. Brescia Morra, Rosa Carbone, A. Filla, Silvio Peluso, Mario Quarantelli, Roberta Lanzillo, Anna Guacci, G. De Michele, Chiara Criscuolo |
|---|---|
| Přispěvatelé: | Criscuolo, Chiara, Carbone, R, Lieto, Maria, Peluso, Silvio, Guacci, A, Filla, Alessandro, Quarantelli, Mario, Lanzillo, Roberta, BRESCIA MORRA, Vincenzo, DE MICHELE, Giuseppe |
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Heterozygote Pathology medicine.medical_specialty spastic paraplegia Adolescent Oxysterol CYP7B1 Cytochrome P450 Family 7 Biology medicine.disease_cause SPG5 Neuroprotection Multiple sclerosis 03 medical and health sciences 0302 clinical medicine Immune system medicine Humans Child Mutation Spastic Paraplegia Hereditary Brain Heterozygote advantage General Medicine Middle Aged medicine.disease 030104 developmental biology Neurology multiple sclerosi Steroid Hydroxylases Female Neurology (clinical) Differential diagnosis 030217 neurology & neurosurgery |
| Zdroj: | Acta neurologica Scandinavica (2015). doi:10.1111/ane.12476 info:cnr-pdr/source/autori:Criscuolo, C.; Carbone, R.; Lieto, M.; Peluso, S.; Guacci, A.; Filla, A.; Quarantelli, M.; Lanzillo, R.; Brescia Morra, V.; De Michele, G./titolo:SPG5 and multiple sclerosis: Clinical and genetic overlap?/doi:10.1111%2Fane.12476/rivista:Acta neurologica Scandinavica/anno:2015/pagina_da:/pagina_a:/intervallo_pagine:/volume Europe PubMed Central |
| DOI: | 10.1111/ane.12476 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|