title: Mutation in cytochrome b gene of mitochondrial DNA in a family with fibromyalgia is associated with NLRP3-inflammasome activation.
abstract: BACKGROUND
  Fibromyalgia (FM) is a worldwide diffuse musculoskeletal chronic pain condition that affects up to 5% of the general population. Many symptoms associated with mitochondrial diseases are reported in patients with FM such as exercise intolerance, fatigue, myopathy and mitochondrial dysfunction. In this study, we report a mutation in cytochrome b gene of mitochondrial DNA (mtDNA) in a family with FM with inflammasome complex activation.
  
  
  METHODS
  mtDNA from blood cells of five patients with FM were sequenced. We clinically and genetically characterised a patient with FM and family with a new mutation in mtCYB. Mitochondrial mutation phenotypes were determined in skin fibroblasts and transmitochondrial cybrids.
  
  
  RESULTS
  After mtDNA sequence in patients with FM, we found a mitochondrial homoplasmic mutation m.15804T>C in the mtCYB gene in a patient and family, which was maternally transmitted. Mutation was observed in several tissues and skin fibroblasts showed a very significant mitochondrial dysfunction and oxidative stress. Increased NLRP3-inflammasome complex activation was observed in blood cells from patient and family.
  
  
  CONCLUSIONS
  We propose further studies on mtDNA sequence analysis in patients with FM with evidences for maternal inheritance. The presence of similar symptoms in mitochondrial myopathies could unmask mitochondrial diseases among patients with FM. On the other hand, the inflammasome complex activation by mitochondrial dysfunction could be implicated in the pathophysiology of mitochondrial diseases.
authors.affiliation: IBiS Institute of Biomedicine of Seville, University Hospital Virgen del Rocío-CSIC-University of Seville, Sevilla, Spain Research Laboratory, Oral Medicine Department, University of Sevilla, Sevilla, Spain.
authors.forename: Mario D
authors.initials: MD
authors.lastname: Cordero
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide-CSIC-Junta de Andalucía, Sevilla, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Sevilla, Spain.
authors.forename: Elísabet
authors.initials: E
authors.lastname: Alcocer-Gómez
authors.affiliation: IBiS Institute of Biomedicine of Seville, University Hospital Virgen del Rocío-CSIC-University of Seville, Sevilla, Spain.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Marín-Aguilar
authors.affiliation: División de Neurociencias, Universidad Pablo de Olavide de Sevilla, Sevilla, Spain.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Rybkina
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide-CSIC-Junta de Andalucía, Sevilla, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Sevilla, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Cotán
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide-CSIC-Junta de Andalucía, Sevilla, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pérez-Pulido
authors.affiliation: Escuela de Medicina Veterinaria y Zootecnia, Facultad de Ciencias de la Salud, Universidad de Las Américas, Quito, Ecuador.
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Alvarez-Suarez
authors.affiliation: Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche-Sez. Biochimica, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Battino
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide-CSIC-Junta de Andalucía, Sevilla, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Sevilla, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Sánchez-Alcazar
authors.affiliation: División de Neurociencias, Universidad Pablo de Olavide de Sevilla, Sevilla, Spain.
authors.forename: Angel M
authors.initials: AM
authors.lastname: Carrión
authors.affiliation: Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
authors.forename: Ognjen
authors.initials: O
authors.lastname: Culic
authors.affiliation: Unidad de Reproducción Humana y Cirugía Endoscópica, Instituto para el Estudio de la Biología de la Reproducción Humana (INEBIR), Sevilla, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Navarro-Pando
authors.affiliation: IBiS Institute of Biomedicine of Seville, University Hospital Virgen del Rocío-CSIC-University of Seville, Sevilla, Spain Research Laboratory, Oral Medicine Department, University of Sevilla, Sevilla, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Bullón
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045303:Cytochromes b / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D005356:Fibromyalgia / Q000235:genetics* / Q000473:pathology; D006801:Humans; D058847:Inflammasomes / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics / Q000473:pathology; D009154:Mutation; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010375:Pedigree
chemical_list: D002352:Carrier Proteins; D004272:DNA, Mitochondrial; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D045303:Cytochromes b
keywords: Immunology (including allergy); Muscle disease