title: Decreased Aerobic Capacity in ANO5-Muscular Dystrophy.
abstract: Anoctaminopathies are muscle diseases caused by recessive mutations in the ANO5 gene. The effects of anoctaminopathy on oxidative capacity have not previously been studied in a controlled setting.
  
  
  
  To characterize oxidative capacity in a clinically and genetically well-defined series of patients with anoctaminopathy.
  
  
  
  We sequenced the ANO5 gene in 111 Finnish patients with suspected LGMD2. Patients with positive findings underwent close clinical examination, including electromyography, muscle MRI, and, in selected cases, muscle biopsy. Oxidative capacity was analyzed using spiroergometry and compared to age-matched healthy controls.
  
  
  
  We characterized 12 newly identified and 2 previously identified patients with ANO5 mutations from 11 families. Our material was genetically homogeneous with most patients homozygous for the Finnish founder variant c.2272C>T (p.Arg758Cys). In one family, we found a novel p.Met470Arg variant compound heterozygous with p.Arg758Cys. Lower limb muscle MRI revealed progressive fatty degeneration of specific posterior compartment muscles. Patients' spiroergometric profiles showed that anoctaminopathy significantly impaired oxidative capacity with increasing ventilation.
  
  
  
  Our findings support earlier reports that anoctaminopathy progresses slowly and demonstrate that the disease impairs the capacity for aerobic exercise.
authors.affiliation: Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.|Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, Finland.
authors.forename: Emil
authors.initials: E
authors.lastname: Ylikallio
authors.affiliation: Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.|Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, Finland.
authors.forename: Mari
authors.initials: M
authors.lastname: Auranen
authors.affiliation: Division of Neurology, Pietarsaari District Hospital, Pietarsaari, Finland.|Department of Neurology, MRC Oulu, Oulu University Hospital and University of Oulu, Finland.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Mahjneh
authors.affiliation: Department of Radiology, HUS Medical Imaging Center, Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Lamminen
authors.affiliation: Folkhälsan Institute of Genetics, Helsinki, Finland.
authors.forename: Maria
authors.initials: M
authors.lastname: Kousi
authors.affiliation: Folkhälsan Institute of Genetics, Helsinki, Finland.
authors.forename: Ann-Liz
authors.initials: AL
authors.lastname: Träskelin
authors.affiliation: Unit of Clinical Physiology, HUS Medical Imaging Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Muurinen
authors.affiliation: Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, Finland.
authors.forename: Mervi
authors.initials: M
authors.lastname: Löfberg
authors.affiliation: Department of Clinical Neurophysiology, Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Tapani
authors.initials: T
authors.lastname: Salmi
authors.affiliation: Department of Pathology, HUSLAB and University of Helsinki, Helsinki, Finland.
authors.forename: Anders
authors.initials: A
authors.lastname: Paetau
authors.affiliation: Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.|Folkhälsan Institute of Genetics, Helsinki, Finland.|Neuroscience Center, University of Helsinki, Finland.
authors.forename: Anna-Elina
authors.initials: AE
authors.lastname: Lehesjoki
authors.affiliation: Unit of Clinical Physiology, HUS Medical Imaging Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Piirilä
authors.affiliation: Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Kiuru-Enari
mesh_terms: D000328:Adult; D000075368:Anoctamins / Q000235:genetics; D016022:Case-Control Studies; D004576:Electromyography; D015444:Exercise / Q000502:physiology; D005080:Exercise Test; D005260:Female; D005387:Finland; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D010101:Oxygen Consumption
chemical_list: C547813:ANO5 protein, human; D000075368:Anoctamins
keywords: Muscular dystrophies; aerobic exercise; inborn genetic diseases; limb-girdle; muscular diseases