Loading...
Please wait, while we are loading the content...
Similar Documents
Does mitochondrial DNA predispose to neuromyelitis optica (Devic's disease)?
| Content Provider | Semantic Scholar |
|---|---|
| Author | Hudson, Gavin Mowbray, Catherine A. Elson, Joanna L. Jacob, Anu Boggild, Michael Torroni, Antonio Chinnery, Patrick F. |
| Copyright Year | 2008 |
| Abstract | Neuromyelitis optica (NMO), or Devic’s disease, is a relapsing demyelinating disease of the central nervous system characterized by optic neuritis and myelitis with distinct clinical, imaging, CSF and serological features (Wingerchuk et al., 2006). There is increasing evidence that NMO is an antibody-mediated organ-specific autoimmune disease associated with anti-aquaporin 4 antibodies detectable in serum (Lennon et al., 2004), supported by four recent papers in the same edition of Brain (Matsuoka et al., 2007; Misu et al., 2007; Roemer et al., 2007; Takahashi et al., 2007) and the accompanying scientific commentary (Compston, 2007). However, it is still not known why the disorder specifically targets the optic nerves and spinal cord. Several siblings with NMO have been reported (McAlpine, 1938; Keegan and Weinshenker, 2000; Yamakawa et al., 2000), raising the possibility of a genetic predisposition, but no pathogenic mutations have been identified in the AQP4 gene on chromosome 18q11.2-q12.1 (Lu et al., 1996). NMO has similarities with Leber hereditary optic neuropathy (LHON, MIM 535 000) which is primarily due to mutations of mitochondrial DNA (mtDNA) that disrupt complex I of the respiratory chain (Carelli et al., 2004). Although the genetic defect in LHON is present in all tissues, the pathology also is strikingly tissue-specific. Most affected individuals develop sub-acute painless visual failure due to focal involvement of both optic nerves (Newman et al., 1991; Riordan-Eva et al., 1995), but some also develop a progressive myelopathy, with high signal extending over multiple spinal levels on MR imaging, and the absence of oligoclonal bands in the CSF (Johns et al., 1991; Jaros et al., 2007). Tissue-specific susceptibility to mitochondrial dysfunction is thought to explain why the neurodegeneration in LHON only affects specific neuronal pathways, and recent evidence implicates a similar mechanism in the axonal loss that follows acute inflammatory lesions in multiple sclerosis (MS) (Dutta et al., 2006). A further link between LHON and central nervous system demyelination is the MS-like illness first described in women harbouring LHON mtDNA mutations (Harding et al., 1992), characterized by severe and often irreversible bilateral visual failure. Patients with LHON-MS have typical brain imaging and unmatched oligoclonal bands in the cerebrospinal fluid (Riordan-Eva et al., 1995). Although the majority of cases are female, males have been described with each of the common LHON mtDNA mutations (Lees et al., 1964; Flanigan and Johns, 1993; Kellar-Wood et al., 1994; Olsen et al., 1995; Jansen et al., 1996; Leuzzi et al., 1997; Horvath et al., 2000; Buhmann et al., 2002). Given the clinical similarities between NMO and LHON, previous investigators have looked for specific mtDNA mutations in a small number of patients with NMO (Johns et al., 1991; Cock et al., 1997; Kalman and Mandler, 2002; Ghezzi et al., 2004), and others have studied polymorphic variation of mtDNA in NMO cases (Cock et al., 1997; Kalman et al., 1999; Kalman and Mandler, 2002; Celebisoy et al., 2006). However, the largest case series only included four patients, so the role of mtDNA in the etiology of NMO has yet to be resolved. To address this issue we studied the mtDNA of 32 British patients with NMO fulfilling recent diagnostic criteria (Wingerchuk et al., 2006). These patients are part of the United Kingdom NMO study cohort co-collected through the British Neurological Surveillance Unit (Jacob et al., 2005). Two different hypotheses were tested: (i) that highly deleterious pathogenic LHON mtDNA mutations are a common cause of NMO; and, (ii) that mtDNA polymorphisms are associated with NMO. We consciously limited our study to patients Brain (2008), 131, e93 |
| Starting Page | e93 |
| Ending Page | e93 |
| Page Count | 1 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://watermark.silverchair.com/awm224.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAacwggGjBgkqhkiG9w0BBwagggGUMIIBkAIBADCCAYkGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM2bxLbWRAEk3LyVQ2AgEQgIIBWi7_tOYFmS_i27HX0lm6IhSwOKbadbtlUlYnljLbxTkzXiH822ABoh2x72wEgqPw9nuK6oFbmd6yf7Rz3J51Gpcgf6bXjzYlWnMAzGbi8h54FaFOHMVcsRzA-OaH5GGyvCdUfX3nNn8tFTn8rc5tBup_vRWSBpIKL_gFdOLxuhqR6HYDjnDd_8baQgE-EtdWJTPpEwy6CuAZAWQ2BISIptKTacxNRKNyhQ6i6T180vaEiL2jAUIVBiBMB2aZajHDDIJBsCvB_ktI6ngc05py7WZJkBYToQj8A0IUIQu3fZwmIX66W_pdblpWISxDmxKsU2i7CHBcld-b7jgwviMxhA0k6DH0-GNc6D8dz3XxKz2BVzWR0ZoiNJf0tgYb-mCLvAkpw1QZjG8qDyhgjs76itUEeak86WxvIi2skmNoB05hnSO8xtOrLGINSsR3D-ShH3uj0i9t4AMcivU |
| Alternate Webpage(s) | https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/brain/131/4/10.1093/brain/awm224/2/awm224.pdf?Expires=1493014574&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q&Signature=G9VpUP7R0O4OcZQWRse4l2UY7qFaaqceAZ5VWnlSPzZWx1Gfml0pY4R2nAzTuz3239k9ehUS~fj6B7tsOP4P4Im2r87F6nmKPW~b0HiXf1l87OSpEq0ThFelWXxtMvIezzO5Sg3NkHyVr77EXY4j3zW5blasIRFrPuBSSEhWiC7q23u4mzCzb2TbWvNBqL9Vtr9uNKJt9zUUtK9KlviNKji5fjcrJ7406DFvRDb7PYv~UesKthd~u22Fy0MAG3w7qscSp7uuGBqh92zViWBmxzzrPYF~GsdolCmq10~43WjqdlHafLJbIP9ItfwppHMeGF3F-u1-aGJ2TLwdgNA6SA__ |
| PubMed reference number | 17967805v1 |
| Volume Number | 131 |
| Part | 4 |
| Journal | Brain : a journal of neurology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | AQP4 gene Autoimmune Diseases Bands Body tissue CNS disorder Cerebrospinal Fluid DNA, Mitochondrial Demyelinating Diseases Demyelination Disorder of the optic nerve Eye GIANT AXONAL NEUROPATHY 1 Genetic Predisposition to Disease Liver Failure, Acute Mitochondrial Diseases Multiple Sclerosis Mutation Myelitis NADH dehydrogenase (ubiquinone) Neuromyelitis Optica Optic Atrophy, Hereditary, Leber Optic Neuritis Paper Parkinson Disease Patients Spinal Cord Diseases diagnostic criteria nervous system disorder water channel |
| Content Type | Text |
| Resource Type | Article |
