title: MPV17 Mutations Causing Adult-Onset Multisystemic Disorder With Multiple Mitochondrial DNA Deletions.
abstract: OBJECTIVE To identify the cause of an adult-onset multisystemic disease with multiple deletions of mitochondrial DNA (mtDNA). DESIGN Case report. SETTING University hospitals. PATIENT A 65-year-old man with axonal sensorimotor peripheral neuropathy, ptosis, ophthalmoparesis, diabetes mellitus, exercise intolerance, steatohepatopathy, depression, parkinsonism, and gastrointestinal dysmotility. RESULTS Skeletal muscle biopsy revealed ragged-red and cytochrome- c oxidase-deficient fibers, and Southern blot analysis showed multiple mtDNA deletions. No deletions were detected in fibroblasts, and the results of quantitative polymerase chain reaction showed that the amount of mtDNA was normal in both muscle and fibroblasts. Exome sequencing using a mitochondrial library revealed compound heterozygous MPV17 mutations (p.LysMet88-89MetLeu and p.Leu143*), a novel cause of mtDNA multiple deletions. CONCLUSIONS In addition to causing juvenile-onset disorders with mtDNA depletion, MPV17 mutations can cause adult-onset multisystemic disease with multiple mtDNA deletions.
authors.forename: Caterina
authors.initials: C
authors.lastname: Garone
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Rubio
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Calvo
authors.forename: Ali
authors.initials: A
authors.lastname: Naini
authors.forename: Kurenai
authors.initials: K
authors.lastname: Tanji
authors.forename: Salvatore
authors.initials: S
authors.lastname: Dimauro
authors.forename: Vamsi K
authors.initials: VK
authors.lastname: Mootha
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano