Document Detail

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.
MedLine Citation:
PMID:  23334599     Owner:  NLM     Status:  MEDLINE    
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(Glu) (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.
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:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neuropathology and experimental neurology     Volume:  72     ISSN:  1554-6578     ISO Abbreviation:  J. Neuropathol. Exp. Neurol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-21     Completed Date:  2013-03-11     Revised Date:  2014-02-24    
Medline Journal Info:
Nlm Unique ID:  2985192R     Medline TA:  J Neuropathol Exp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  164-75     Citation Subset:  IM    
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MeSH Terms
Ataxia / complications,  genetics*,  pathology
Brain / pathology
Cataract / complications,  genetics*,  pathology
DNA Mutational Analysis
Electron Transport Complex I / deficiency*,  genetics
Magnetic Resonance Imaging
Middle Aged
Mitochondrial Proteins / deficiency
Mutation / genetics*
Optic Nerve / pathology
Paraparesis, Spastic / complications,  genetics*,  pathology
RNA, Transfer, Glu / genetics*
Grant Support
096919//Wellcome Trust; 906919//Wellcome Trust; G0400074//Medical Research Council; G0502157//Medical Research Council; G0700718//Medical Research Council; G0900652//Medical Research Council; //Biotechnology and Biological Sciences Research Council
Reg. No./Substance:
0/Mitochondrial Proteins; 0/RNA, Transfer, Glu; EC Transport Complex I

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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