title: SCA28: Novel Mutation in the AFG3L2 Proteolytic Domain Causes a Mild Cerebellar Syndrome with Selective Type-1 Muscle Fiber Atrophy.
abstract: The spinocerebellar ataxias (SCA) are a group of rare inherited neurodegenerative diseases characterized by slowly progressive cerebellar ataxia, resulting in unsteady gait, clumsiness, and dysarthria. The disorders are predominantly inherited in an autosomal dominant manner. Mutations in the gene AFG3L2 that encodes a subunit of the mitochondrial m-AAA protease have previously been shown to cause spinocerebellar ataxia type 28 (SCA28). Here, we present the clinical phenotypes of three patients from a family with autosomal dominant cerebellar ataxia and show by molecular genetics and in silico modelling that this is caused by a novel missense mutation in the AFG3L2 gene. Furthermore, we show, for the first time, fluorodeoxyglucose-positron emission tomography (FDG-PET) scans of the brain and selective type I fiber atrophy of skeletal muscle of SCA28 patients indicating non-nervous-system involvement in SCA28 as well.
authors: Danish Dementia Research Centre, Neurogenetics Clinic, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.|Department of Cellular and Molecular Medicine, Section of Neurogenetics, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.|Copenhagen Neuromuscular Center and Clinic, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: Kirsten
authors: K
authors: Svenstrup
authors: Neurogenetics Research Laboratory, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Troels.Tolstrup.Nielsen@regionh.dk.
authors: Troels Tolstrup
authors: TT
authors: Nielsen
authors: Department of Cellular and Molecular Medicine, Section of Neurogenetics, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
authors: Frederik
authors: F
authors: Aidt
authors: Neurogenetics Research Laboratory, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: Nina
authors: N
authors: Rostgaard
authors: Department of Clinical Genetics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: Morten
authors: M
authors: Duno
authors: Department of Clinical Genetics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: Flemming
authors: F
authors: Wibrand
authors: Danish Dementia Research Centre, Neurogenetics Clinic, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.|Department of Cellular and Molecular Medicine, Section of Neurogenetics, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
authors: Tua
authors: T
authors: Vinther-Jensen
authors: Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: Ian
authors: I
authors: Law
authors: Copenhagen Neuromuscular Center and Clinic, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: John
authors: J
authors: Vissing
authors: Danish Dementia Research Centre, Neurogenetics Clinic, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: Peter
authors: P
authors: Roos
authors: Danish Dementia Research Centre, Neurogenetics Clinic, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.|Department of Cellular and Molecular Medicine, Section of Neurogenetics, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
authors: Lena Elisabeth
authors: LE
authors: Hjermind
authors: Danish Dementia Research Centre, Neurogenetics Clinic, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.|Department of Cellular and Molecular Medicine, Section of Neurogenetics, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.|Neurogenetics Research Laboratory, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: Jørgen Erik
authors: JE
authors: Nielsen
mesh_terms: D049069:ATP-Dependent Proteases / Q000235:genetics*; D000074183:ATPases Associated with Diverse Cellular Activities; D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002524:Cerebellar Ataxia / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018657:Muscle Fibers, Slow-Twitch / Q000473:pathology*; D020125:Mutation, Missense; D010641:Phenotype; D000072417:Protein Domains
chemical_list: D049069:ATP-Dependent Proteases; C120699:AFG3L2 protein, human; D000074183:ATPases Associated with Diverse Cellular Activities
keywords: ADCA; AGF3L2; FDG-PET; Muscle; SCA; SCA28