| Early-Onset Cataracts, Spastic Paraparesis, and Ataxia Caused by a Novel Mitochondrial tRNAGlu (MT-TE) Gene Mutation Causing Severe Complex I Deficiency: A Clinical, Molecular, and Neuropathologic Study. | |
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MedLine Citation:
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PMID: 23334599 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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ABSTRACT: Mitochondrial respiratory chain disease is associated with a spectrum of clinical presentations and considerable genetic heterogeneity. Here we report molecular genetic and neuropathologic findings from an adult with an unusual manifestation of mitochondrial DNA disease. Clinical features included early-onset cataracts, ataxia, and progressive paraparesis, with sequencing revealing the presence of a novel de novo m.14685G>A mitochondrial tRNA (MT-TE) gene mutation. Muscle biopsy showed that 13% and 34% of muscle fibers lacked cytochrome c oxidase activity and complex I subunit expression, respectively. Biochemical studies confirmed a marked decrease in complex I activity. Neuropathologic investigation revealed a large cystic lesion affecting the left putamen, caudate nucleus, and internal capsule, with evidence of marked microvacuolation, neuron loss, perivascular lacunae, and blood vessel mineralization. The internal capsule showed focal axonal loss, whereas brainstem and spinal cord showed descending anterograde degeneration in medullary pyramids and corticospinal tracts. In agreement with muscle biopsy findings, reduced complex I immunoreactivity was detected in the remaining neuronal populations, particularly in the basal ganglia and cerebellum, correlating with the neurologic dysfunction exhibited by the patient. This study emphasizes the importance of molecular genetic and postmortem neuropathologic analyses for furthering our understanding of underlying mechanisms of mitochondrial disorders. |
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Authors:
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Nichola Z Lax; Sharmilee Gnanapavan; Sarah J Dowson; Charlotte L Alston; Langping He; Tuomo M Polvikoski; Evelyn Jaros; Dominic G O'Donovan; John W Yarham; Douglass M Turnbull; Andrew F Dean; Robert W Taylor |
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Publication Detail:
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Type: JOURNAL ARTICLE |
Journal Detail:
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Title: Journal of neuropathology and experimental neurology Volume: 72 ISSN: 1554-6578 ISO Abbreviation: J. Neuropathol. Exp. Neurol. Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-1-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985192R Medline TA: J Neuropathol Exp Neurol Country: - |
Other Details:
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Languages: ENG Pagination: 164-175 Citation Subset: - |
Affiliation:
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From the Wellcome Trust Centre for Mitochondrial Research (NZL, SJD, CLA, LH, JWY, DMT, RWT), and Newcastle University Centre for Brain Ageing and Vitality (NZL, DMT), Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle upon Tyne; Department of Neuroimmunology, Institute of Neurology, Queen Square, London (SG); Neuropathology/Cellular Pathology, Royal Victoria Infirmary, Queen Victoria Road (TMP, EJ); Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality (TMP, EJ); and UK NIHR Biomedical Research Centre for Ageing and Age-related Disease Award to the Newcastle upon Tyne Hospitals NHS Foundation Trust (EJ), Newcastle upon Tyne; Department of Histopathology, Addenbrooke's Hospital, Cambridge (DGO, AFD); and Department of Cellular Pathology, Queen's Hospital, Romford (DGO), UK. |
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